Materiały źródłowe

• #1 Acute Rheumatic Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594238/

  Acute rheumatic fever (ARF) is an abnormal immunologic response to group A Streptococcus (GAS) infections, most commonly tonsillopharyngitis. […] The pathophysiology of ARF is characterized by an aberrant immune response to GAS infection triggered by molecular mimicry between GAS antigens and self-antigens. This immune response typically manifests 2 to 4 weeks after the initial GAS infection and may lead to the development of carditis, valvulitis, Sydenham chorea, subcutaneous nodules, erythema marginatum, and polyarthritis that is usually migratory. […] The pathophysiology of ARF is incompletely understood but thought to be multifactorial. Preceding GAS infection is necessary for the development of ARF. Additionally, host factors and repeated exposures to GAS contribute to the pathogenesis of ARF.

• #2 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  The pathogenic mechanisms of ARF are not completely understood. Studies of the pathogenesis of ARF have been constrained by the lack of a highly suitable animal model, although a Lewis rat model of valvulitis and chorea has been used for some time. In order for ARF to occur, it appears that a pharyngeal infection caused by S. pyogenes must occur in a host with a genetic susceptibility to the disease. […] Activation of the innate immune system begins with a pharyngeal infection that leads to the presentation of S. pyogenes antigens to T and B cells. CD4+ T cells are activated and production of specific IgG and IgM antibody by B cells ensues. Tissue injury is mediated through an immune-mediated mechanism that is initiated via molecular mimicry. Structural similarity between the infectious agent and human proteins leads to the cross-activation of antibodies and/or T cells directed against human proteins. In ARF, this cross-reactive immune response results in the clinical features of rheumatic fever, including carditis, due to antibody binding and infiltration of T cells; transient arthritis, due to the formation of immune complexes; chorea, due to the binding of antibodies to basal ganglia; and skin manifestations, due to a delayed hypersensitivity reaction.

• #3 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The pathogenesis of ARF and rheumatic heart disease is complex and not fully understood. It involves bacterial factors, host susceptibility, molecular mimicry, and aberrant innate and adaptive immune responses in the host. […] Molecular mimicry is thought to account for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues. […] Streptococcal antigens that are structurally similar to those in the heart include hyaluronate in the bacterial capsule, cell wall polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share epitopes with the sarcolemma and smooth muscle. Studies have shown a correlation between antibodies against streptolysin O, a cytolytic toxin elaborated by group A streptococci, and antibodies against human cardiac myosin.

• #4 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strep throat infection, specifically due to group A streptococcus (GAS), Streptococcus pyogenes. The similarity between antigens of Streptococcus pyogenes and multiple cardiac proteins can cause a life-threatening type II hypersensitivity reaction. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+ T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

• #5 Acute Rheumatic Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594238/

  In molecular mimicry, antibodies formed against GAS antigens crossreact with self-antigens, leading to a dysregulated immune response. A variety of GAS antigens are implicated in molecular mimicry. The M protein moiety and N-acetyl–D-glucosamine (NABG) of GAS species exhibit structural similarity to myosin, leading to cardiac myositis and valvulitis. […] Host susceptibility to ARF is likely polygenic. Monozygotic twin studies demonstrate a 40% concordance risk for ARF. Human leukocyte antigen alleles and tumor necrosis factor polymorphisms play a role in genetic susceptibility to ARF.

• #6 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever. […] The researchers concluded that the high proportion of differentially expressed apoptotic and immune response genes supports a model of autoimmune and cytokine dysregulation in ARF. […] ARF often produces a pancarditis, characterized by endocarditis, myocarditis, and pericarditis. Endocarditis manifests as mitral and aortic valve insufficiency. Severe scarring of the valves develops during a period of months to years after an episode of ARF, and recurrent episodes may cause progressive damage to the valves. […] Whether myocardial dysfunction during ARF is primarily related to myocarditis or is secondary to CHF from severe valve insufficiency is not known. […] Chronic manifestations occur in adults from residual and progressive valve deformity. Rheumatic heart disease is responsible for 99% of mitral valve stenosis in adults, and it may be associated with atrial fibrillation from chronic mitral valve disease.

• #7 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  There are a number of lines of evidence that suggest molecular mimicry plays a role in the development of carditis by stimulating both humoral and cellular cross-reactive immune responses. The alpha-helical protein structures found in M protein and N-acetyl-beta-D-glucosamine (the carbohydrate antigen of S. pyogenes) share epitopes with myosin, and antibodies against both of these antigens cross-react against human tissues. Monoclonal antibodies generated from tonsillar or peripheral blood lymphocytes of patients infected with S. pyogenes cross-react with myosin. Monoclonal antibodies directed against myosin and N-acetyl-beta-D-glucosamine isolated react against human valvular endothelium in patients with rheumatic fever. In a Lewis rat model, immunization with recombinant streptococcal M protein type 6 led to development valvulitis.

• #8 Rheumatic Fever | Thoracic Key

  https://thoracickey.com/rheumatic-fever/

  Rheumatic fever is a multifactorial disease that follows GAS pharyngitis (the agent) in a susceptible individual (the host) who lives under deprived social conditions (the environment). The theory of molecular mimicry holds that GAS pharyngitis triggers an autoimmune response to epitopes in the organism that cross-react with similar epitopes in the heart, brain, joints, and skin, and repeated episodes of rheumatic fever lead to rheumatic heart disease. […] Epidemiologic and immunologic observations together with the preventive effect of antibiotic treatment of pharyngitis demonstrated in clinical trials strongly support the causative role of untreated GAS pharyngitis in rheumatic fever. […] Cunningham reviewed the hypothesis of molecular mimicry in the pathogenesis of rheumatic fever. There is evidence that patients with rheumatic heart disease have cross-reactive autoantibodies that target the dominant GAS epitope of the group A carbohydrate N-acetyl-beta-d-glucosamine (GlcNAc), as well as laminin and the laminar basement membrane in heart valve endothelium.

• #9 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The pathogenesis of ARF and rheumatic heart disease is complex and not fully understood. It involves bacterial factors, host susceptibility, molecular mimicry, and aberrant innate and adaptive immune responses in the host. […] Molecular mimicry is thought to account for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues. […] Streptococcal antigens that are structurally similar to those in the heart include hyaluronate in the bacterial capsule, cell wall polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share epitopes with the sarcolemma and smooth muscle. Studies have shown a correlation between antibodies against streptolysin O, a cytolytic toxin elaborated by group A streptococci, and antibodies against human cardiac myosin.

• #10 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The pathogenesis of ARF and rheumatic heart disease is complex and not fully understood. It involves bacterial factors, host susceptibility, molecular mimicry, and aberrant innate and adaptive immune responses in the host. […] Molecular mimicry is thought to account for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues. […] Streptococcal antigens that are structurally similar to those in the heart include hyaluronate in the bacterial capsule, cell wall polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share epitopes with the sarcolemma and smooth muscle. Studies have shown a correlation between antibodies against streptolysin O, a cytolytic toxin elaborated by group A streptococci, and antibodies against human cardiac myosin.

• #11 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The pathogenesis of ARF and rheumatic heart disease is complex and not fully understood. It involves bacterial factors, host susceptibility, molecular mimicry, and aberrant innate and adaptive immune responses in the host. […] Molecular mimicry is thought to account for the tissue injury that occurs in rheumatic fever. Both the humoral and cellular host defenses of a genetically vulnerable host are involved. In this process, the patient’s immune responses (both B- and T-cell mediated) are unable to distinguish between the invading microbe and certain host tissues. […] Streptococcal antigens that are structurally similar to those in the heart include hyaluronate in the bacterial capsule, cell wall polysaccharides (similar to glycoproteins in heart valves), and membrane antigens that share epitopes with the sarcolemma and smooth muscle. Studies have shown a correlation between antibodies against streptolysin O, a cytolytic toxin elaborated by group A streptococci, and antibodies against human cardiac myosin.

• #12 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  There are a number of lines of evidence that suggest molecular mimicry plays a role in the development of carditis by stimulating both humoral and cellular cross-reactive immune responses. The alpha-helical protein structures found in M protein and N-acetyl-beta-D-glucosamine (the carbohydrate antigen of S. pyogenes) share epitopes with myosin, and antibodies against both of these antigens cross-react against human tissues. Monoclonal antibodies generated from tonsillar or peripheral blood lymphocytes of patients infected with S. pyogenes cross-react with myosin. Monoclonal antibodies directed against myosin and N-acetyl-beta-D-glucosamine isolated react against human valvular endothelium in patients with rheumatic fever. In a Lewis rat model, immunization with recombinant streptococcal M protein type 6 led to development valvulitis.

• #13 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  The pathogenic mechanisms of ARF are not completely understood. Studies of the pathogenesis of ARF have been constrained by the lack of a highly suitable animal model, although a Lewis rat model of valvulitis and chorea has been used for some time. In order for ARF to occur, it appears that a pharyngeal infection caused by S. pyogenes must occur in a host with a genetic susceptibility to the disease. […] Activation of the innate immune system begins with a pharyngeal infection that leads to the presentation of S. pyogenes antigens to T and B cells. CD4+ T cells are activated and production of specific IgG and IgM antibody by B cells ensues. Tissue injury is mediated through an immune-mediated mechanism that is initiated via molecular mimicry. Structural similarity between the infectious agent and human proteins leads to the cross-activation of antibodies and/or T cells directed against human proteins. In ARF, this cross-reactive immune response results in the clinical features of rheumatic fever, including carditis, due to antibody binding and infiltration of T cells; transient arthritis, due to the formation of immune complexes; chorea, due to the binding of antibodies to basal ganglia; and skin manifestations, due to a delayed hypersensitivity reaction.

• #14 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Rheumatic-heart-disease-pathophysiology.aspx

  The first step is a pharyngeal infection with Streptococcus pyogenes, followed by the presentation of antigens to the immune T and B cells. […] Activation of CD4+ cells leads to the production of specific acute and chronic phase antibodies (IgM and IgG, respectively) by B lymphocytes. […] These antibodies and activated T cells react with structurally similar proteins or peptides in heart tissue, which is called cross-reaction. As a result, the heart becomes inflamed. […] The overexpression of VCAM-1 molecules causes CD4+ cells to stick to and burrow into the valve endothelium, activating a cellular immune response in the valve. This produces an inflammation of the valve tissue with the growth of new blood vessels. […] While this is the accepted mechanism of RHD, newer research is focusing on the endothelium covering the heart valves as the target of immunologic damage in this condition.

• #15 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  The pathogenic mechanisms of ARF are not completely understood. Studies of the pathogenesis of ARF have been constrained by the lack of a highly suitable animal model, although a Lewis rat model of valvulitis and chorea has been used for some time. In order for ARF to occur, it appears that a pharyngeal infection caused by S. pyogenes must occur in a host with a genetic susceptibility to the disease. […] Activation of the innate immune system begins with a pharyngeal infection that leads to the presentation of S. pyogenes antigens to T and B cells. CD4+ T cells are activated and production of specific IgG and IgM antibody by B cells ensues. Tissue injury is mediated through an immune-mediated mechanism that is initiated via molecular mimicry. Structural similarity between the infectious agent and human proteins leads to the cross-activation of antibodies and/or T cells directed against human proteins. In ARF, this cross-reactive immune response results in the clinical features of rheumatic fever, including carditis, due to antibody binding and infiltration of T cells; transient arthritis, due to the formation of immune complexes; chorea, due to the binding of antibodies to basal ganglia; and skin manifestations, due to a delayed hypersensitivity reaction.

• #16

  https://biomedres.us/fulltexts/BJSTR.MS.ID.004793.php

  Rheumatic heart disease (RHD) is damage of the heart valves due to acute rheumatic fever (ARF) which results from the bodys autoimmune response to Streptococcus pyogenes (group A Streptococcus bacteria) infection which is a throat infection. […] Autoimmune reactions in ARF and RHD are caused by molecular mimicry between Streptococcus pyogenes antigens and human proteins which is a type II hypersensitivity. […] During streptococcal infection, antigen presenting cells such as dendritic cells and B cells present the streptococcal antigens to nave CD4+ T cell and lead to activation to helper T cell. […] Activated B cells in the germinal centers differentiate into plasma cells which then produce antibodies which are part of a normal humoral response against S. pyogenes bacteria. However, the antibodies produced cross react with antigens in heart tissue or joints which lead to neutrophil and macrophage activation and inflammation.

• #17 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strep throat infection, specifically due to group A streptococcus (GAS), Streptococcus pyogenes. The similarity between antigens of Streptococcus pyogenes and multiple cardiac proteins can cause a life-threatening type II hypersensitivity reaction. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+ T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

• #18 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strep throat infection, specifically due to group A streptococcus (GAS), Streptococcus pyogenes. The similarity between antigens of Streptococcus pyogenes and multiple cardiac proteins can cause a life-threatening type II hypersensitivity reaction. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+ T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

• #19

  https://biomedres.us/fulltexts/BJSTR.MS.ID.004793.php

  Rheumatic heart disease (RHD) is damage of the heart valves due to acute rheumatic fever (ARF) which results from the bodys autoimmune response to Streptococcus pyogenes (group A Streptococcus bacteria) infection which is a throat infection. […] Autoimmune reactions in ARF and RHD are caused by molecular mimicry between Streptococcus pyogenes antigens and human proteins which is a type II hypersensitivity. […] During streptococcal infection, antigen presenting cells such as dendritic cells and B cells present the streptococcal antigens to nave CD4+ T cell and lead to activation to helper T cell. […] Activated B cells in the germinal centers differentiate into plasma cells which then produce antibodies which are part of a normal humoral response against S. pyogenes bacteria. However, the antibodies produced cross react with antigens in heart tissue or joints which lead to neutrophil and macrophage activation and inflammation.

• #20 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.

• #21 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Rheumatic fever is a systemic disease affecting the connective tissue around arterioles, and can occur after an untreated strep throat infection, specifically due to group A streptococcus (GAS), Streptococcus pyogenes. The similarity between antigens of Streptococcus pyogenes and multiple cardiac proteins can cause a life-threatening type II hypersensitivity reaction. Usually, self reactive B cells remain anergic in the periphery without T cell co-stimulation. During a streptococcal infection, mature antigen-presenting cells such as B cells present the bacterial antigen to CD4+ T cells which differentiate into helper T2 cells. Helper T2 cells subsequently activate the B cells to become plasma cells and induce the production of antibodies against the cell wall of Streptococcus. However the antibodies may also react against the myocardium and joints, producing the symptoms of rheumatic fever.

• #22 Acute rheumatic fever – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/acute-rheumatic-fever/

  Acute rheumatic fever (ARF) is an inflammatory sequela involving the heart, joints, skin, and central nervous system (CNS) that occurs two to four weeks after an untreated group A hemolytic streptococcal infection (GAS). The pathogenic mechanisms that cause rheumatic fever are not completely understood, but molecular mimicry between streptococcal M protein and human cardiac myosin proteins is thought to play a role. […] Because of the structural similarities between the two proteins, antibodies and T cells activated to respond to streptococcal proteins also react with the human proteins, causing tissue injury and inflammation. […] The exact pathogenesis is not yet entirely understood. Most commonly accepted mechanism involves the following: acute tonsillitis/pharyngitis caused by GAS without antibiotic treatment development of antibodies against streptococcal M protein cross-reaction of antibodies with nerve and myocardial proteins (most commonly myosins) due to molecular mimicry type II hypersensitivity reaction acute inflammatory sequela.

• #23 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #24 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #25 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #26

  https://biomedres.us/fulltexts/BJSTR.MS.ID.004793.php

  Molecular mimicry in ARF occurs due to the alpha-helical protein structures found in M protein and N-acetyl-beta-Dglucosamine which is the carbohydrate antigen of S. pyogenes cross react with cardiac myosin, myocardium and valves. […] Binding of cross-reactive antibodies causes upregulation of vascular cell adhesion molecule 1 which results in adherence of CD4+ T cells to the endothelium and subsequently the cells enter the valve. […] Inflammation occurs when T-cells release -IFN due to TH1 response which will lead to neovascularization and further T-cells recruitment. […] T cells infiltrate the heart valves and result in scarring due to inflammation of the endothelium surrounding the valve. […] Besides that, autoantibodies against type I collagen are also produced can be caused by aggregation of collagen by certain streptococcal serotypes or damaged valve which release collagen in rheumatic heart disease.

• #27 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #28 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #29 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #30

  https://biomedres.us/fulltexts/BJSTR.MS.ID.004793.php

  Molecular mimicry in ARF occurs due to the alpha-helical protein structures found in M protein and N-acetyl-beta-Dglucosamine which is the carbohydrate antigen of S. pyogenes cross react with cardiac myosin, myocardium and valves. […] Binding of cross-reactive antibodies causes upregulation of vascular cell adhesion molecule 1 which results in adherence of CD4+ T cells to the endothelium and subsequently the cells enter the valve. […] Inflammation occurs when T-cells release -IFN due to TH1 response which will lead to neovascularization and further T-cells recruitment. […] T cells infiltrate the heart valves and result in scarring due to inflammation of the endothelium surrounding the valve. […] Besides that, autoantibodies against type I collagen are also produced can be caused by aggregation of collagen by certain streptococcal serotypes or damaged valve which release collagen in rheumatic heart disease.

• #31 Acute Rheumatic Fever and Rheumatic Heart Disease – Streptococcus pyogenes – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK425394/

  Human heart intralesional T cell clones react against cardiac tissues, including myosin and valve-derived proteins. Autoreactive T cells appear to play an important role in granulomatous inflammation in cardiac valves. Vascular cell adhesion molecule 1 may be the link between humoral and cellular immunity at the valve surface. Vascular cell adhesion molecule 1 is upregulated at the valve endothelium surface as a result of binding of cross-reactive antibodies. This leads to adherence of CD4+ T cells to the endothelium, with subsequent infiltration of these cells into the valve. The T-cells initiate a predominantly TH1 response with the release of -IFN. Inflammation leads to neovascularization, which allows further recruitment of T-cells. Epitope spreading may occur in the valve, where T-cells respond against other cardiac proteins such as vimentin and tropomyosin and lead to the formation of granulomatous lesions underneath the endocardium (Aschoff bodies).

• #32 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.

• #33 Acute Rheumatic Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594238/

  In molecular mimicry, antibodies formed against GAS antigens crossreact with self-antigens, leading to a dysregulated immune response. A variety of GAS antigens are implicated in molecular mimicry. The M protein moiety and N-acetyl–D-glucosamine (NABG) of GAS species exhibit structural similarity to myosin, leading to cardiac myositis and valvulitis. […] Host susceptibility to ARF is likely polygenic. Monozygotic twin studies demonstrate a 40% concordance risk for ARF. Human leukocyte antigen alleles and tumor necrosis factor polymorphisms play a role in genetic susceptibility to ARF.

• #34 Acute Rheumatic Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594238/

  In molecular mimicry, antibodies formed against GAS antigens crossreact with self-antigens, leading to a dysregulated immune response. A variety of GAS antigens are implicated in molecular mimicry. The M protein moiety and N-acetyl–D-glucosamine (NABG) of GAS species exhibit structural similarity to myosin, leading to cardiac myositis and valvulitis. […] Host susceptibility to ARF is likely polygenic. Monozygotic twin studies demonstrate a 40% concordance risk for ARF. Human leukocyte antigen alleles and tumor necrosis factor polymorphisms play a role in genetic susceptibility to ARF.

• #35 Acute Rheumatic Fever – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK594238/

  In molecular mimicry, antibodies formed against GAS antigens crossreact with self-antigens, leading to a dysregulated immune response. A variety of GAS antigens are implicated in molecular mimicry. The M protein moiety and N-acetyl–D-glucosamine (NABG) of GAS species exhibit structural similarity to myosin, leading to cardiac myositis and valvulitis. […] Host susceptibility to ARF is likely polygenic. Monozygotic twin studies demonstrate a 40% concordance risk for ARF. Human leukocyte antigen alleles and tumor necrosis factor polymorphisms play a role in genetic susceptibility to ARF.

• #36 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration. […] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a host’s susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response.

• #37 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration. […] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a host’s susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response.

• #38 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration. […] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a host’s susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response.

• #39 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration. […] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a host’s susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response.

• #40 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever. […] The researchers concluded that the high proportion of differentially expressed apoptotic and immune response genes supports a model of autoimmune and cytokine dysregulation in ARF. […] ARF often produces a pancarditis, characterized by endocarditis, myocarditis, and pericarditis. Endocarditis manifests as mitral and aortic valve insufficiency. Severe scarring of the valves develops during a period of months to years after an episode of ARF, and recurrent episodes may cause progressive damage to the valves. […] Whether myocardial dysfunction during ARF is primarily related to myocarditis or is secondary to CHF from severe valve insufficiency is not known. […] Chronic manifestations occur in adults from residual and progressive valve deformity. Rheumatic heart disease is responsible for 99% of mitral valve stenosis in adults, and it may be associated with atrial fibrillation from chronic mitral valve disease.

• #41 Acute Rheumatic Fever: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/236582-overview

  The resultant inflammation may persist well beyond the acute infection and produces the protean manifestations of rheumatic fever. […] The researchers concluded that the high proportion of differentially expressed apoptotic and immune response genes supports a model of autoimmune and cytokine dysregulation in ARF. […] ARF often produces a pancarditis, characterized by endocarditis, myocarditis, and pericarditis. Endocarditis manifests as mitral and aortic valve insufficiency. Severe scarring of the valves develops during a period of months to years after an episode of ARF, and recurrent episodes may cause progressive damage to the valves. […] Whether myocardial dysfunction during ARF is primarily related to myocarditis or is secondary to CHF from severe valve insufficiency is not known. […] Chronic manifestations occur in adults from residual and progressive valve deformity. Rheumatic heart disease is responsible for 99% of mitral valve stenosis in adults, and it may be associated with atrial fibrillation from chronic mitral valve disease.

• #42

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  Despite identifying that rheumatic fever (RF) is the result of an immunological reaction following group-A beta-hemolytic streptococcal infection, the pathogenesis remains elusive. […] RF causes permanent damage to cardiac valves. […] Evaluation of the histopathology and immunopathology indicates that RF is a disease of the valvular and vascular endothelium. It is not a connective tissue disorder. Research to identify pathogenesis needs to be focused toward valvular endothelium. […] The primary site of RF damage appears to be endothelium with its basement membrane. […] The pathological findings of RF provide clues to the pathophysiology of RF. RF is characterized by proliferative and exudative inflammation involving primarily collagen tissue or its ground substance. There is a pronounced tendency to affect tissues lined by endothelium, including blood vessels, endocardium, pericardium, and synovia.

• #43

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #44

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  Despite identifying that rheumatic fever (RF) is the result of an immunological reaction following group-A beta-hemolytic streptococcal infection, the pathogenesis remains elusive. […] RF causes permanent damage to cardiac valves. […] Evaluation of the histopathology and immunopathology indicates that RF is a disease of the valvular and vascular endothelium. It is not a connective tissue disorder. Research to identify pathogenesis needs to be focused toward valvular endothelium. […] The primary site of RF damage appears to be endothelium with its basement membrane. […] The pathological findings of RF provide clues to the pathophysiology of RF. RF is characterized by proliferative and exudative inflammation involving primarily collagen tissue or its ground substance. There is a pronounced tendency to affect tissues lined by endothelium, including blood vessels, endocardium, pericardium, and synovia.

• #45 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as „bread-and-butter” pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular damage. […] The complicated pathogenesis of RHD is not fully understood, though it has been observed to use molecular mimicry via group A streptococci carbohydrates and genetic predisposition involving HLA Class II genes that trigger autoimmune reactions. Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as „foreign” due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD.

• #46 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as „bread-and-butter” pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular damage. […] The complicated pathogenesis of RHD is not fully understood, though it has been observed to use molecular mimicry via group A streptococci carbohydrates and genetic predisposition involving HLA Class II genes that trigger autoimmune reactions. Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as „foreign” due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD.

• #47 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as „bread-and-butter” pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular damage. […] The complicated pathogenesis of RHD is not fully understood, though it has been observed to use molecular mimicry via group A streptococci carbohydrates and genetic predisposition involving HLA Class II genes that trigger autoimmune reactions. Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as „foreign” due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD.

• #48 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as „bread-and-butter” pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A -hemolytic streptococci (GAS) that results in valvular damage. […] The complicated pathogenesis of RHD is not fully understood, though it has been observed to use molecular mimicry via group A streptococci carbohydrates and genetic predisposition involving HLA Class II genes that trigger autoimmune reactions. Molecular mimicry occurs when epitopes are shared between host antigens and Streptococcus antigens. This causes an autoimmune reaction against native tissues in the heart that are incorrectly recognized as „foreign” due to the cross-reactivity of antibodies generated as a result of epitope sharing. The valvular endothelium is a prominent site of lymphocyte-induced damage. CD4+ T cells are the major effectors of heart tissue autoimmune reactions in RHD.

• #49 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  Normally, T cell activation is triggered by the presentation of bacterial antigens. In RHD, molecular mimicry results in incorrect T cell activation, and these T lymphocytes can go on to activate B cells, which will begin to produce self-antigen-specific antibodies. This leads to an immune response attack mounted against tissues in the heart that have been misidentified as pathogens. Rheumatic valves display increased expression of VCAM-1, a protein that mediates the adhesion of lymphocytes. Self-antigen-specific antibodies generated via molecular mimicry between human proteins and streptococcal antigens up-regulate VCAM-1 after binding to the valvular endothelium. This leads to the inflammation and valve scarring observed in rheumatic valvulitis, mainly due to CD4+ T cell infiltration. […] While the mechanisms of genetic predisposition remain unclear, a few genetic factors have been found to increase susceptibility to autoimmune reactions in RHD. The dominant contributors are a component of MHC class II molecules, found on lymphocytes and antigen-presenting cells, specifically the DR and DQ alleles on human chromosome 6. Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a host’s susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response.

• #50

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #51 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.

• #52 Rheumatic fever – Wikipedia

  https://en.wikipedia.org/wiki/Rheumatic_fever

  S. pyogenes has a cell wall composed of branched polymers which sometimes contain M protein, a virulence factor that is highly antigenic. The antibodies which the immune system generates against the M protein may cross-react with heart muscle cell protein myosin, heart muscle glycogen and smooth muscle cells of arteries, inducing cytokine release and tissue destruction. However, the only proven cross-reaction is with perivascular connective tissue. This inflammation occurs through direct attachment of complement and Fc receptor-mediated recruitment of neutrophils and macrophages. Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.

• #53

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #54

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #55

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #56

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #57

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #58

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #59

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #60

  https://journals.lww.com/aopc/fulltext/2012/05020/rheumatic_fever_pathogenesis__approach_in_research.10.aspx

  The hallmark of RF carditis is the Aschoff nodule (AN). […] Therefore, it can safely be concluded that the AN, the hallmark of rheumatic carditis, is not derived from myocardial damage. […] The absence of myocarditis has been demonstrated and documented by (1) the absence of increase in markers of myocardial damage (CK-MB, Troponin-I), (2) echocardiographic left ventricular function studies, (3) radionuclide imaging (technetium pyrophosphate, indium111, antimyosin fab), (4) myocardial biopsy studies, (5) surgical management during active carditis, (6) histopathology and immunopathology. […] Since RF does not cause myocardial damage, and the fact that congestive failure occurs only in the presence of severe mitral and/or aortic regurgitation, it is possible to conclude that rheumatic valvulitis causing acute and chronic valvular damage determines the morbidity and mortality of RF. […] The data presented suggest that the site of disease appears to be the valvar and vascular endothelium. The causative antigen needs to be identified and cannot be assumed to be GAS M-protein.

• #61 The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease

  https://www.mdpi.com/1422-0067/23/24/15812

  The study of a Lewis rat model of rheumatic carditis revealed that M protein-specific T cells acted as key mediators of valvulitis. […] The presence of inflammation and oxidative stress has been suggested to be involved in the pathogenesis of rheumatic heart valve disease. Higher levels of soluble factors in patients with active RHD compared to those with latent states indicate greater activation of the immune system in the first group. The infection with group A streptococcus (GAS) can induce delayed autoimmune response which results in ARF, while a recurrent or continuing autoimmune inflammatory response against self-antigens appears to be the trigger involved in the pathogenesis of autoimmune-driven RHD. […] The mechanisms of pattern recognition of GAS antigens by human immune cells are not fully clear. It has been found that GAS-related M proteins, peptidoglycans and nucleic acids can stimulate the macrophages to release proinflammatory cytokines, including interleukin (IL)-1β and tumour necrosis factor (TNF).

• #62 The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease

  https://www.mdpi.com/1422-0067/23/24/15812

  The study of a Lewis rat model of rheumatic carditis revealed that M protein-specific T cells acted as key mediators of valvulitis. […] The presence of inflammation and oxidative stress has been suggested to be involved in the pathogenesis of rheumatic heart valve disease. Higher levels of soluble factors in patients with active RHD compared to those with latent states indicate greater activation of the immune system in the first group. The infection with group A streptococcus (GAS) can induce delayed autoimmune response which results in ARF, while a recurrent or continuing autoimmune inflammatory response against self-antigens appears to be the trigger involved in the pathogenesis of autoimmune-driven RHD. […] The mechanisms of pattern recognition of GAS antigens by human immune cells are not fully clear. It has been found that GAS-related M proteins, peptidoglycans and nucleic acids can stimulate the macrophages to release proinflammatory cytokines, including interleukin (IL)-1β and tumour necrosis factor (TNF).

• #63 The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease

  https://www.mdpi.com/1422-0067/23/24/15812

  The study of a Lewis rat model of rheumatic carditis revealed that M protein-specific T cells acted as key mediators of valvulitis. […] The presence of inflammation and oxidative stress has been suggested to be involved in the pathogenesis of rheumatic heart valve disease. Higher levels of soluble factors in patients with active RHD compared to those with latent states indicate greater activation of the immune system in the first group. The infection with group A streptococcus (GAS) can induce delayed autoimmune response which results in ARF, while a recurrent or continuing autoimmune inflammatory response against self-antigens appears to be the trigger involved in the pathogenesis of autoimmune-driven RHD. […] The mechanisms of pattern recognition of GAS antigens by human immune cells are not fully clear. It has been found that GAS-related M proteins, peptidoglycans and nucleic acids can stimulate the macrophages to release proinflammatory cytokines, including interleukin (IL)-1β and tumour necrosis factor (TNF).

• #64 The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease

  https://www.mdpi.com/1422-0067/23/24/15812

  The study of a Lewis rat model of rheumatic carditis revealed that M protein-specific T cells acted as key mediators of valvulitis. […] The presence of inflammation and oxidative stress has been suggested to be involved in the pathogenesis of rheumatic heart valve disease. Higher levels of soluble factors in patients with active RHD compared to those with latent states indicate greater activation of the immune system in the first group. The infection with group A streptococcus (GAS) can induce delayed autoimmune response which results in ARF, while a recurrent or continuing autoimmune inflammatory response against self-antigens appears to be the trigger involved in the pathogenesis of autoimmune-driven RHD. […] The mechanisms of pattern recognition of GAS antigens by human immune cells are not fully clear. It has been found that GAS-related M proteins, peptidoglycans and nucleic acids can stimulate the macrophages to release proinflammatory cytokines, including interleukin (IL)-1β and tumour necrosis factor (TNF).

• #65 The Role of Inflammation and Oxidative Stress in Rheumatic Heart Disease

  https://www.mdpi.com/1422-0067/23/24/15812

  The study of a Lewis rat model of rheumatic carditis revealed that M protein-specific T cells acted as key mediators of valvulitis. […] The presence of inflammation and oxidative stress has been suggested to be involved in the pathogenesis of rheumatic heart valve disease. Higher levels of soluble factors in patients with active RHD compared to those with latent states indicate greater activation of the immune system in the first group. The infection with group A streptococcus (GAS) can induce delayed autoimmune response which results in ARF, while a recurrent or continuing autoimmune inflammatory response against self-antigens appears to be the trigger involved in the pathogenesis of autoimmune-driven RHD. […] The mechanisms of pattern recognition of GAS antigens by human immune cells are not fully clear. It has been found that GAS-related M proteins, peptidoglycans and nucleic acids can stimulate the macrophages to release proinflammatory cytokines, including interleukin (IL)-1β and tumour necrosis factor (TNF).

• #66 Revisiting the pathogenesis of rheumatic fever and carditis | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2012.197

  Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial -helical coiled-coil proteins. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein N-terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome. […] Proposed pathogenesis of rheumatic fever.

• #67 Revisiting the pathogenesis of rheumatic fever and carditis | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2012.197

  Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial -helical coiled-coil proteins. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein N-terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome. […] Proposed pathogenesis of rheumatic fever.

• #68 Revisiting the pathogenesis of rheumatic fever and carditis | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2012.197

  Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial -helical coiled-coil proteins. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein N-terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome. […] Proposed pathogenesis of rheumatic fever.

• #69 Revisiting the pathogenesis of rheumatic fever and carditis | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2012.197

  Rheumatic fever is one of the most-neglected ailments, and its pathogenesis remains poorly understood. The major thrust of research has been directed towards cross-reactivity between streptococcal M protein and myocardial -helical coiled-coil proteins. The characteristic pathological findings suggest that the primary site of rheumatic-fever-related damage is subendothelial and perivascular connective tissue matrix and overlying endothelium. Over the past 5 years, a streptococcal M protein N-terminus domain has been shown to bind to the CB3 region in collagen type IV. This binding seems to initiate an antibody response to the collagen and result in ground substance inflammation. These antibodies do not cross-react with M proteins, and we believe that no failure of immune system and, possibly, no molecular mimicry occur in rheumatic fever. This alternative hypothesis shares similarity with collagen involvement in both Goodpasture syndrome and Alport syndrome. […] Proposed pathogenesis of rheumatic fever.

• #70 Project MUSE – The Pathogenesis of Rheumatic Fever—a Concept

  https://muse.jhu.edu/article/406016/summary

  THE PATHOGENESIS OF RHEUMATIC FEVERA CONCEPT ALVINF. COBURN, M.D.* […] The hypothesis is that lipids protect against activity of the rheumatic process. […] Moreover, the concept that lipids have a protective role is now of more than academic interest; gas chromatography has developed to a degree that the hypothesis can be tested. […] It now seems clear that a relatively new method, gas chromatography, may permit an attack on the role of lipids at a point where rheumatic fever research has long been stymied. […] Insufficient information is the hallmark of rheumatic fever research. […] It is this continual shifting of the many variables in rheumatic fever that attracts the adventuresome explorer.

• #71 Project MUSE – The Pathogenesis of Rheumatic Fever—a Concept

  https://muse.jhu.edu/article/406016/summary

  THE PATHOGENESIS OF RHEUMATIC FEVERA CONCEPT ALVINF. COBURN, M.D.* […] The hypothesis is that lipids protect against activity of the rheumatic process. […] Moreover, the concept that lipids have a protective role is now of more than academic interest; gas chromatography has developed to a degree that the hypothesis can be tested. […] It now seems clear that a relatively new method, gas chromatography, may permit an attack on the role of lipids at a point where rheumatic fever research has long been stymied. […] Insufficient information is the hallmark of rheumatic fever research. […] It is this continual shifting of the many variables in rheumatic fever that attracts the adventuresome explorer.

• #72 Recent Advances in the Rheumatic Fever and Rheumatic Heart Disease Continuum

  https://www.mdpi.com/2076-0817/11/2/179

  The consensus remains that immune-mediated pathology is the hallmark of RHD. […] Traditional dogma holds that GAS pharyngitis is responsible for triggering the immune reaction that leads to RHD pathology. […] However, more recently, other superficial streptococcal infections, such as impetigo and pyoderma, have been associated with RHD. […] There is also emerging evidence potentially implicating group C and group G streptococcus in contributing to the pathogenesis of RHD. […] The most widely accepted hypothesis in the pathogenesis of RF/RHD is molecular mimicry, but more recent data suggests a more complex cascade of events, such as the hypothesis of collagen-associated neo-antigens and additional mechanisms such as epitope spreading and T cell receptor (TCR) degeneracy that may participate in pathology.

• #73 Recent Advances in the Rheumatic Fever and Rheumatic Heart Disease Continuum

  https://www.mdpi.com/2076-0817/11/2/179

  Additionally, specific CD4+ T cells, as well as NK cells and CD4-CD8- T cells, might be important players in tissue destruction in RHD. […] Recent efforts have been developed to take advantage of the intense response triggered by GAS antigens toward the establishment of vaccines, which have remained elusive largely due to lack of investment. […] Dissecting the immunopathogenic responses using state-of-the-art methods such as single cell RNA sequencing combined with TCR CDR3 region usage may open new insights to advance this field.

• #74 Potential Role of Vitamin D in Pathogenesis of Acute Rheumatic Fever | ESPE2016 | 55th Annual ESPE (ESPE 2016) | ESPE Abstracts

  https://abstracts.eurospe.org/hrp/0086/hrp0086p2-p172

  Potential Role of Vitamin D in Pathogenesis of Acute Rheumatic Fever […] The underlying mechanisms have not been fully elucidated. A series of autoimmune processes are thought to be involved in pathogenesis. […] 25(OH)D levels was found lower in patients with ARF suggesting potential role of vitamin D deficiency in development of ARF.

• #75

  https://link.springer.com/article/10.1007/BF02041393

  Immunopathologic studies were performed on heart tissue of patients with acute rheumatic fever with carditis and chronic rheumatic heart disease. […] These findings suggested that Coxsackie group B virus may be etiologically related to the pathogenesis of acute rheumatic fever.

• #76

  https://journals.lww.com/hhmi/fulltext/2024/08020/neurobehavioral_changes_associated_with_rheumatic.5.aspx

  Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune conditions triggered by Group A Streptococcus skin or throat infections. […] While the precise mechanism as to why only a proportion of patients with ARF/RHD develop SC remains unknown, an impaired blood-brain barrier is considered to play a central role in its development. […] The poststreptococcal autoimmune responses that lead to ARF/RHD are multifactorial. It is known that antibodies and T-cells generated against GAS M-protein and N-acetyl-beta-D-glucosamine cross-react with host tissue proteins, a hallmark of ARF/RHD immunopathogenesis. […] Antibodies against GAS N-acetyl-beta-D-glucosamine are known to cross-react with neuronal cells in the basal ganglia, leading to the deposition of immune complexes causing excessive release of dopamine that forms the basis of the symptomatology observed in SC, a neurobehavioral abnormality that is observed in patients with ARF/RHD.

• #77

  https://journals.lww.com/hhmi/fulltext/2024/08020/neurobehavioral_changes_associated_with_rheumatic.5.aspx

  Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are autoimmune conditions triggered by Group A Streptococcus skin or throat infections. […] While the precise mechanism as to why only a proportion of patients with ARF/RHD develop SC remains unknown, an impaired blood-brain barrier is considered to play a central role in its development. […] The poststreptococcal autoimmune responses that lead to ARF/RHD are multifactorial. It is known that antibodies and T-cells generated against GAS M-protein and N-acetyl-beta-D-glucosamine cross-react with host tissue proteins, a hallmark of ARF/RHD immunopathogenesis. […] Antibodies against GAS N-acetyl-beta-D-glucosamine are known to cross-react with neuronal cells in the basal ganglia, leading to the deposition of immune complexes causing excessive release of dopamine that forms the basis of the symptomatology observed in SC, a neurobehavioral abnormality that is observed in patients with ARF/RHD.

• #78

  https://journals.lww.com/hhmi/fulltext/2024/08020/neurobehavioral_changes_associated_with_rheumatic.5.aspx

  A compromised blood-brain barrier (BBB) is a possible link. During systemic inflammation and infection such as ARF, many circulating soluble inflammatory mediators could influence BBB permeability. […] Recent studies in our laboratory (unpublished observation) using adoptive transfer of hyperimmune serum from GAS M5-injected rats confirmed the importance of a compromised BBB in the development of neurobehavioral changes associated with ARF. […] Antibodies against GAS cross-react with dopamine receptor I, II and neural proteins tubulin and lysoganglioside in the basal ganglia. […] These antibodies activate CaMKII and also bind to lysoganglioside or DR1 and DR2 on neuronal surface possibly leading to alterations in dopamine transmission.

• #79

  https://journals.lww.com/hhmi/fulltext/2024/08020/neurobehavioral_changes_associated_with_rheumatic.5.aspx

  A compromised blood-brain barrier (BBB) is a possible link. During systemic inflammation and infection such as ARF, many circulating soluble inflammatory mediators could influence BBB permeability. […] Recent studies in our laboratory (unpublished observation) using adoptive transfer of hyperimmune serum from GAS M5-injected rats confirmed the importance of a compromised BBB in the development of neurobehavioral changes associated with ARF. […] Antibodies against GAS cross-react with dopamine receptor I, II and neural proteins tubulin and lysoganglioside in the basal ganglia. […] These antibodies activate CaMKII and also bind to lysoganglioside or DR1 and DR2 on neuronal surface possibly leading to alterations in dopamine transmission.

• #80

  https://journals.lww.com/hhmi/fulltext/2024/08020/neurobehavioral_changes_associated_with_rheumatic.5.aspx

  A compromised blood-brain barrier (BBB) is a possible link. During systemic inflammation and infection such as ARF, many circulating soluble inflammatory mediators could influence BBB permeability. […] Recent studies in our laboratory (unpublished observation) using adoptive transfer of hyperimmune serum from GAS M5-injected rats confirmed the importance of a compromised BBB in the development of neurobehavioral changes associated with ARF. […] Antibodies against GAS cross-react with dopamine receptor I, II and neural proteins tubulin and lysoganglioside in the basal ganglia. […] These antibodies activate CaMKII and also bind to lysoganglioside or DR1 and DR2 on neuronal surface possibly leading to alterations in dopamine transmission.

• #81 Acute rheumatic fever and rheumatic heart disease | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201584

  Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. […] Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. […] Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. […] This study of mAbs from human rheumatic carditis explain the mimicry between group A streptococcal antigens and the heart valves and myocardium. Specific cross-reactive antigens included the group A carbohydrate and -helical proteins such as cardiac myosin in the myocardium and laminin in the endocardium of the valve. […] This article provides guidance on the Doppler and two-dimensional echocardiographic findings that are consistent with RHD. The criteria are based on consensus international expert opinion and available evidence and have been crucial for the field in standardizing diagnosis across centres.

• #82 Acute rheumatic fever and rheumatic heart disease | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201584

  Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. […] Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. […] Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. […] This study of mAbs from human rheumatic carditis explain the mimicry between group A streptococcal antigens and the heart valves and myocardium. Specific cross-reactive antigens included the group A carbohydrate and -helical proteins such as cardiac myosin in the myocardium and laminin in the endocardium of the valve. […] This article provides guidance on the Doppler and two-dimensional echocardiographic findings that are consistent with RHD. The criteria are based on consensus international expert opinion and available evidence and have been crucial for the field in standardizing diagnosis across centres.

• #83 Rheumatic Fever: Causes, Symptoms (Rash) & Treatment

  https://my.clevelandclinic.org/health/diseases/16616-rheumatic-fever

  Rheumatic fever is an autoimmune condition that inflames your childs tissues, such as their joints and heart. […] Rheumatic fever is a rare autoimmune disease that causes inflammation of your childs tissues and organs. […] An untreated strep throat or scarlet fever infection can trigger this overreaction. It happens when your child doesnt receive antibiotic treatment for group A Streptococcus infections. […] When your bodys defenses (antibodies) begin to fight back, the reaction can damage healthy tissues and organs instead of the bacteria. […] Rheumatic fever treatment first focuses on getting rid of the bacterial infection. Treatments then address inflammation inside your childs body. […] Rheumatic fever can come back or become a serious problem. In some cases, rheumatic fever can lead to serious or even life-threatening complications.

• #84

  https://www.who.int/news-room/fact-sheets/detail/rheumatic-heart-disease

  Rheumatic heart disease results from damage to heart valves caused by one or several episodes of rheumatic fever, an autoimmune inflammatory reaction to throat infection caused by group A streptococci (streptococcal pharyngitis or strep throat). […] In some people, this streptococcal infection causes the immune system to react against the tissues of the body including inflaming and scarring the heart valves. This is referred to as rheumatic fever. Rheumatic heart disease results from the inflammation and scarring of heart valves caused by rheumatic fever. […] Since rheumatic heart disease results from rheumatic fever, an important strategy is to prevent rheumatic fever from occurring. Treatment of strep throat with appropriate antibiotics will prevent rheumatic fever. […] A steady supply of benzathine penicillin G is an essential prerequisite for treatment of sore throat and to prevent recurrent infection. However, the antibiotic is prone to global shortages.

• #85 Rheumatic Fever: Causes, Symptoms (Rash) & Treatment

  https://my.clevelandclinic.org/health/diseases/16616-rheumatic-fever

  Rheumatic fever is an autoimmune condition that inflames your childs tissues, such as their joints and heart. […] Rheumatic fever is a rare autoimmune disease that causes inflammation of your childs tissues and organs. […] An untreated strep throat or scarlet fever infection can trigger this overreaction. It happens when your child doesnt receive antibiotic treatment for group A Streptococcus infections. […] When your bodys defenses (antibodies) begin to fight back, the reaction can damage healthy tissues and organs instead of the bacteria. […] Rheumatic fever treatment first focuses on getting rid of the bacterial infection. Treatments then address inflammation inside your childs body. […] Rheumatic fever can come back or become a serious problem. In some cases, rheumatic fever can lead to serious or even life-threatening complications.

Zobacz więcej