Materiały źródłowe

• #1 Pathogenesis of IgA Vasculitis: An Up-To-Date Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8630619/

  Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schnlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. […] Identification of environmental and genetic factors and recognition of aberrant IgA may shed light on the pathogenesis of IgAV. […] Aberrant IgA and IgA complexes are considered to play a central role in the immunopathogenesis of IgAV. […] The mechanism of pathogen or mucosal antigen-related IgAV is unclear; however, theoretically, it can be pointed to the modulation of mucosal immunity, including galactose-deficient IgA1 (Gd-IgA1) production. […] A widely accepted hypothesis for the pathogenesis for IgAN is a multi-hit model proposed by Novak J. et al. In this model, the first and second hit is the production of Gd-IgA1 and autoantibodies against Gd-IgA1, the third hit is the formation of Gd-IgA1 containing immune complexes, and finally, the fourth hit is the deposition of immune complexes in tissue activates the inflammatory process that results in organ injury.

• #2

  https://link.springer.com/article/10.1007/s00467-009-1230-x

  The severity of renal involvement is the major factor determining the long-term outcome of children with Henoch-Schnlein purpura (HSP) nephritis (HSPN). Approximately 40% children with HSP develop nephritis, usually within 4 to 6 weeks after the initial onset of the typical purpuric rashes. […] Although the pathogenetic mechanisms are still not fully delineated, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of the circulating immune complexes and their mesangial deposition that induce renal injury in HSPN. […] The postulation that HSPN is a systemic immune-complex mediated disease is supported by the clinical or histological recurrences of HSPN in some patients after transplantation. […] Although detailed pathogenic mechanisms of HSPN have not been fully elucidated, perturbations in the immune system, including elevations in serum levels of IgA1, IgA1-containing circulating immune complexes and IgA-rheumatoid factors have been documented for patients with HSP.

• #3 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  IgA clearly plays a critical role in the immunopathogenesis of IgAV, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls of affected organs and in the kidney mesangium. Deposition of IgA aggregates or IgA complexes in target organs occurs with activation of the alternative complement pathway (with deposition of C3). This results in elaboration of inflammatory mediators, including vascular prostaglandins such as prostacyclin, that may play a central role in the pathogenesis of IgAV and its organ-specific clinical manifestations. […] IgA is found in the serum and mucosal secretions and is a major class of immunoglobulins that plays an important role in mucosal immunity. IgAV is almost exclusively associated with abnormalities involving IgA1, rather than IgA2. IgA1 is phylogenetically younger and differs from IgA2 by the insertion of a 13-17 amino acid sequence in the hinge region of the IgA1 molecule.

• #4 Henoch-Schonlein Purpura: IgA vasculitis – Creative Med Doses

  https://creativemeddoses.com/topics-list/henoch-schonlein-purpura-iga-vasculitis/

  Henoch-Schnlein purpura (HSP) is also called IgA vasculitis, it is a small-vessel vasculitis characterized by palpable purpura, arthralgias, abdominal pain and hematuria. […] The central pathogenic mechanism for Henoch-Schnlein purpura/ IgA vasculitis is immune-complex deposition. Henoch-Schnlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules. It is a type III hypersensitivity reaction. […] HSP is a type of hypersensitivity vasculitis where inflammatory mediators such as Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process. Transforming growth factor (TGF) is a recognized stimulant of IgA production. […] IgA plays a critical role in the immunopathogenesis of HSP. There are increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls and renal mesangium of cases presenting with HSP. […] IgA aggregates or IgA complexes with complement deposited in target organs, resulting in secretion of inflammatory mediators, including vascular prostaglandins such as prostacyclin, which plays a central role in the pathogenesis of HSP vasculitis.

• #5 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  IgA clearly plays a critical role in the immunopathogenesis of IgAV, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls of affected organs and in the kidney mesangium. Deposition of IgA aggregates or IgA complexes in target organs occurs with activation of the alternative complement pathway (with deposition of C3). This results in elaboration of inflammatory mediators, including vascular prostaglandins such as prostacyclin, that may play a central role in the pathogenesis of IgAV and its organ-specific clinical manifestations. […] IgA is found in the serum and mucosal secretions and is a major class of immunoglobulins that plays an important role in mucosal immunity. IgAV is almost exclusively associated with abnormalities involving IgA1, rather than IgA2. IgA1 is phylogenetically younger and differs from IgA2 by the insertion of a 13-17 amino acid sequence in the hinge region of the IgA1 molecule.

• #6 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  The predominance of IgA1 in IgAV may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the IgA1 hinge region. Patients with IgAV and IgA nephritis express inherited galactose-deficient glycosylation of IgA1 molecules. […] IgAV-associated nephritis is characterized by an abnormal IgA1 glycosylation pattern with reduced galactosylation. […] The hinge region of IgA1 contains up to six major glycosylation sites at serine and threonine residues. The O-glycans include a core N-acetylgalactosamine (GalNAc), which is usually extended with galactose to form Gal1,3GalNAc, which can bind to N-acetylneuraminic acid (Neu5Ac). Thus, each IgA1 O-glycan can have one of four short carbohydrate structures (types III, IV, V, and VI), leading to a mixture of IgA1 forms with varying degrees of galactosylation.

• #7 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  The predominance of IgA1 in IgAV may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the IgA1 hinge region. Patients with IgAV and IgA nephritis express inherited galactose-deficient glycosylation of IgA1 molecules. […] IgAV-associated nephritis is characterized by an abnormal IgA1 glycosylation pattern with reduced galactosylation. […] The hinge region of IgA1 contains up to six major glycosylation sites at serine and threonine residues. The O-glycans include a core N-acetylgalactosamine (GalNAc), which is usually extended with galactose to form Gal1,3GalNAc, which can bind to N-acetylneuraminic acid (Neu5Ac). Thus, each IgA1 O-glycan can have one of four short carbohydrate structures (types III, IV, V, and VI), leading to a mixture of IgA1 forms with varying degrees of galactosylation.

• #8 Pathogenesis of IgA Vasculitis: An Up-To-Date Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8630619/

  Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schnlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. […] Identification of environmental and genetic factors and recognition of aberrant IgA may shed light on the pathogenesis of IgAV. […] Aberrant IgA and IgA complexes are considered to play a central role in the immunopathogenesis of IgAV. […] The mechanism of pathogen or mucosal antigen-related IgAV is unclear; however, theoretically, it can be pointed to the modulation of mucosal immunity, including galactose-deficient IgA1 (Gd-IgA1) production. […] A widely accepted hypothesis for the pathogenesis for IgAN is a multi-hit model proposed by Novak J. et al. In this model, the first and second hit is the production of Gd-IgA1 and autoantibodies against Gd-IgA1, the third hit is the formation of Gd-IgA1 containing immune complexes, and finally, the fourth hit is the deposition of immune complexes in tissue activates the inflammatory process that results in organ injury.

• #9 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Patients with IgAV-associated nephritis have a high prevalence of galactose-deficient (types I and II) IgA1. […] The lack of terminal 1,3-galactosyl residues in the hinge region of IgA might be due to the reduced activity of 1,3-galactosyltransferase in IgA1-producing peripheral B cells. This reduction of galactosylation results in the exposure of GalNAc residues in the IgA1 surface, forming a novel antigen and inducing a humoral IgG autoimmune response. […] Circulating complexes of mixed IgG and galactose-deficient IgA1 are detected in patients with IgAV, and also in the serum of patients with mucosal infections. […] The finding that galactose-deficient IgA1 molecules are found in IgAV only during an episode of nephritis lends support to the pathophysiologic role of galactose-deficient IgA1 molecules in IgAV nephritis.

• #10 Henoch-Schönlein purpura pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Henoch-Sch%C3%B6nlein_purpura_pathophysiology

  It has been reported that in patients with HSP, the activity of 1,3-galactosyltransferase in peripheral B cells is reduced, leading to a lack of terminal 1,3-galactosyl residues in the hinge region of IgA1. […] These aberrantly glycosylated IgA1 molecules have been shown to form immune complexes with IgG antibodies specific for galactose-deficient IgA1, thereby inhibiting the binding of the IgA molecules to hepatic receptors and avoiding their internalization and degradation by hepatic cells. […] The complexes may then deposit in renal mesangial areas and activate the complement system by the alternative or lectin pathways, which play a major role in the pathophysiology of this disease. […] Further, after depositing in the mesangium, the galactose-deficient IgA1 immune complexes activate mesangial cells.

• #11 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Patients with IgAV-associated nephritis have a high prevalence of galactose-deficient (types I and II) IgA1. […] The lack of terminal 1,3-galactosyl residues in the hinge region of IgA might be due to the reduced activity of 1,3-galactosyltransferase in IgA1-producing peripheral B cells. This reduction of galactosylation results in the exposure of GalNAc residues in the IgA1 surface, forming a novel antigen and inducing a humoral IgG autoimmune response. […] Circulating complexes of mixed IgG and galactose-deficient IgA1 are detected in patients with IgAV, and also in the serum of patients with mucosal infections. […] The finding that galactose-deficient IgA1 molecules are found in IgAV only during an episode of nephritis lends support to the pathophysiologic role of galactose-deficient IgA1 molecules in IgAV nephritis.

• #12 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Patients with IgAV-associated nephritis have a high prevalence of galactose-deficient (types I and II) IgA1. […] The lack of terminal 1,3-galactosyl residues in the hinge region of IgA might be due to the reduced activity of 1,3-galactosyltransferase in IgA1-producing peripheral B cells. This reduction of galactosylation results in the exposure of GalNAc residues in the IgA1 surface, forming a novel antigen and inducing a humoral IgG autoimmune response. […] Circulating complexes of mixed IgG and galactose-deficient IgA1 are detected in patients with IgAV, and also in the serum of patients with mucosal infections. […] The finding that galactose-deficient IgA1 molecules are found in IgAV only during an episode of nephritis lends support to the pathophysiologic role of galactose-deficient IgA1 molecules in IgAV nephritis.

• #13 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  IgA clearly plays a critical role in the immunopathogenesis of IgAV, as evidenced by increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls of affected organs and in the kidney mesangium. Deposition of IgA aggregates or IgA complexes in target organs occurs with activation of the alternative complement pathway (with deposition of C3). This results in elaboration of inflammatory mediators, including vascular prostaglandins such as prostacyclin, that may play a central role in the pathogenesis of IgAV and its organ-specific clinical manifestations. […] IgA is found in the serum and mucosal secretions and is a major class of immunoglobulins that plays an important role in mucosal immunity. IgAV is almost exclusively associated with abnormalities involving IgA1, rather than IgA2. IgA1 is phylogenetically younger and differs from IgA2 by the insertion of a 13-17 amino acid sequence in the hinge region of the IgA1 molecule.

• #14 Henoch–Schönlein purpura – Wikipedia

  https://en.wikipedia.org/wiki/Henoch%E2%80%93Sch%C3%B6nlein_purpura

  Henoch–Schönlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules (hence it is a type III hypersensitivity reaction). The activation of the alternative complement pathway results in the deposition of IgA aggregates or IgA complexes in target organs (with deposition of C3). […] This leads to the production of inflammatory mediators, including vascular prostaglandins like prostacyclin, which may play a key role in the development of IgAV and its organ-specific clinical manifestations. […] The genetic basis remains unclear except for involvement of the human leukocyte antigen region of the genome. […] It is hypothesized to involve autoimmunity triggered by infections. Streptococcus strains and Parainfluenza virus are the most commonly associated pathogens, and in children Human Parvovirus B19 is a frequent viral trigger.

• #15 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  Activation of the alternative and lectin pathways of the complement system by the Gd-IgA1 ICs also plays a relevant role. Elevated deposits of complement components such as C3a, C5a, C4, and the membrane attack complex (C5b-9) are found in IgAV patients, and their presence correlates with disease severity, especially in cases involving renal complications. […] The activation of T-cells and B-cells is also relevant. […] Environmental triggers may promote the development of the IgAV. Mucosal infections often precede IgAV onset, and several pathogens have been implicated in triggering the disease, such as viruses (Hepatitis B or parvovirus) or bacteria, among which Streptococcus, Staphylococcus or Helicobacter pylori stand out. […] Genetic susceptibility has been described in patients with IgAV.

• #16 The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120411

  The complement was mainly activated through the alternative pathway in our HSP patients. […] C3a and C5a are small protein fragments released from the cleavage of C3 and C5. Their plasma levels in HSP patients were high at the acute stage and significantly declined when HSP was in remission. […] In summary, our current study indicated the activation of alternative pathway in HSP based on the elevated plasma levels of C3a, C5a, and Bb, but not C4a in HSP patients at the acute stage.

• #17 The Interaction between Circulating Complement Proteins and Cutaneous Microvascular Endothelial Cells in the Development of Childhood Henoch-Schönlein Purpura | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120411

  The complement was mainly activated through the alternative pathway in our HSP patients. […] C3a and C5a are small protein fragments released from the cleavage of C3 and C5. Their plasma levels in HSP patients were high at the acute stage and significantly declined when HSP was in remission. […] In summary, our current study indicated the activation of alternative pathway in HSP based on the elevated plasma levels of C3a, C5a, and Bb, but not C4a in HSP patients at the acute stage.

• #18 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  However, there is no evidence supporting a direct role of herpesvirus or retrovirus infection in the pathogenesis of IgAV. […] Alterations in the production of interleukins (ILs) and growth factors may also play a pathogenetic role. Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process present in IgAV. Transforming growth factor (TGF) is a recognized stimulant of IgA production. The elevated levels of hepatocyte growth factor present during the acute phase of IgAV may reflect endothelial-cell damage or dysfunction. Increased levels of vascular endothelial growth factor (VEGF) may at least partly induce these changes. […] Cytokines have been implicated in the pathogenesis of IgAV, and endothelins (ETs), which are vasoconstrictor hormones produced by endothelial cells, may also have a role. Levels of ET-1 are substantially higher during the acute phase of the disease than during remission or in healthy children. However, ET-1 levels do not appear to correlate with morbidity, severity of disease, or acute-phase reactant response.

• #19 Henoch-Schonlein Purpura: IgA vasculitis – Creative Med Doses

  https://creativemeddoses.com/topics-list/henoch-schonlein-purpura-iga-vasculitis/

  Henoch-Schnlein purpura (HSP) is also called IgA vasculitis, it is a small-vessel vasculitis characterized by palpable purpura, arthralgias, abdominal pain and hematuria. […] The central pathogenic mechanism for Henoch-Schnlein purpura/ IgA vasculitis is immune-complex deposition. Henoch-Schnlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules. It is a type III hypersensitivity reaction. […] HSP is a type of hypersensitivity vasculitis where inflammatory mediators such as Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process. Transforming growth factor (TGF) is a recognized stimulant of IgA production. […] IgA plays a critical role in the immunopathogenesis of HSP. There are increased serum IgA concentrations, IgA-containing circulating immune complexes, and IgA deposition in vessel walls and renal mesangium of cases presenting with HSP. […] IgA aggregates or IgA complexes with complement deposited in target organs, resulting in secretion of inflammatory mediators, including vascular prostaglandins such as prostacyclin, which plays a central role in the pathogenesis of HSP vasculitis.

• #20 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  However, there is no evidence supporting a direct role of herpesvirus or retrovirus infection in the pathogenesis of IgAV. […] Alterations in the production of interleukins (ILs) and growth factors may also play a pathogenetic role. Tumor necrosis factor (TNF), IL-1, and IL-6 may mediate the inflammatory process present in IgAV. Transforming growth factor (TGF) is a recognized stimulant of IgA production. The elevated levels of hepatocyte growth factor present during the acute phase of IgAV may reflect endothelial-cell damage or dysfunction. Increased levels of vascular endothelial growth factor (VEGF) may at least partly induce these changes. […] Cytokines have been implicated in the pathogenesis of IgAV, and endothelins (ETs), which are vasoconstrictor hormones produced by endothelial cells, may also have a role. Levels of ET-1 are substantially higher during the acute phase of the disease than during remission or in healthy children. However, ET-1 levels do not appear to correlate with morbidity, severity of disease, or acute-phase reactant response.

• #21 Henoch-Schönlein purpura pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Henoch-Sch%C3%B6nlein_purpura_pathophysiology

  This results in the proliferation of cells such as macrophages and lymphocytes and the production of inflammatory and profibrogenic cytokines and chemokines, which play a pivotal role in mesangial cell proliferation, matrix expansion, and inflammatory cell recruitment. […] Activation of the eosinophils and expression of the alpha-smooth muscle actin in the kidney also play a vital role in the pathogenesis of Henoch-Schnlein purpura.

• #22 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Although several lines of evidence suggest a genetic susceptibility to IgAV, the fundamental basis for this abnormality remains unclear. A functional correlation of the IL1RN-2 allele and IL-1ra production in patients with IgA nephropathy and IgAV nephritis has been described. Therefore, gene polymorphism may contribute to the diversity of clinical responses to inflammatory stimulation. The prevalence of the human parvovirus B19 component NS1 gene in patients with IgAV and hypersensitivity vasculitis is increased. […] Gershoni-Baruch et al showed that in the Israeli population, 10% of patients with IgAV were homozygous for mutations in MEFV (the gene defective in familial Mediterranean fever that encodes the protein pyrin/marenostrin, which regulates caspase-1 activation and IL-1b production). An additional 17% of patients with IgAV had heterozygous defects of this gene.

• #23 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Peru et al reported an increased risk of IgAV in children carrying HLA A2, A11, and B35 antigens and a reduced risk in those carrying HLA A1, B49, and B50 antigens. […] Researchers are currently investigating the importance of nitric oxide (NO) production in disease activity. Inducible NO synthase polymorphism has been associated with susceptibility to IgAV in northwestern Spain. Aliyazicioglu et al have suggested that leptin and NO may play a role in the immunoinflammatory process of IgAV, especially in the acute phase. […] Yilmaz et al examined markers of hypercoagulability in 28 children with IgAV and 79 healthy children, and found that levels of fibrinogen, D-dimer, thrombin-antithrombin (TAT) complex, prothrombin fragment (PF)-1, PF-2, and von Willebrand factor antigen (vWAg) and its activity (RiCof) were significantly higher during the acute phase than during the recovery phase and were significantly higher in patients with IgAV than in control subjects. […] The severity of disease correlated significantly with TAT, PF-1, PF-2, vWAg, and D-dimer levels. Higher levels of matrix metalloproteinase9 (MMP-9) in urine and serum appear to correlate with increased nephrologic severity in children with IgAV.

• #24 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  Peru et al reported an increased risk of IgAV in children carrying HLA A2, A11, and B35 antigens and a reduced risk in those carrying HLA A1, B49, and B50 antigens. […] Researchers are currently investigating the importance of nitric oxide (NO) production in disease activity. Inducible NO synthase polymorphism has been associated with susceptibility to IgAV in northwestern Spain. Aliyazicioglu et al have suggested that leptin and NO may play a role in the immunoinflammatory process of IgAV, especially in the acute phase. […] Yilmaz et al examined markers of hypercoagulability in 28 children with IgAV and 79 healthy children, and found that levels of fibrinogen, D-dimer, thrombin-antithrombin (TAT) complex, prothrombin fragment (PF)-1, PF-2, and von Willebrand factor antigen (vWAg) and its activity (RiCof) were significantly higher during the acute phase than during the recovery phase and were significantly higher in patients with IgAV than in control subjects. […] The severity of disease correlated significantly with TAT, PF-1, PF-2, vWAg, and D-dimer levels. Higher levels of matrix metalloproteinase9 (MMP-9) in urine and serum appear to correlate with increased nephrologic severity in children with IgAV.

• #25 Henoch-Schönlein Purpura (IgA Vasculitis): Rapid Evidence Review | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/0815/p229.html

  Henoch-Schnlein purpura, now called immunoglobulin A (IgA) vasculitis, is a systemic, immune complex-mediated, small-vessel leukocytoclastic vasculitis characterized by nonthrombocytopenic palpable purpura, arthritis, and abdominal pain. […] IgA vasculitis is a small-vessel vasculitis caused by IgA immune deposits in the gastrointestinal system, joints, skin, and kidneys. […] Multiple viral and bacterial infections are thought to trigger the disease, including Streptococcus, parainfluenza, and human parvovirus B19. Cytokines and chemokines are involved; however, the full pathophysiology is not understood. […] Numerous studies have linked disease predisposition, severity, and long-term morbidity with genes on portions of the HLA alleles.

• #26 Henoch–Schönlein purpura – Wikipedia

  https://en.wikipedia.org/wiki/Henoch%E2%80%93Sch%C3%B6nlein_purpura

  Henoch–Schönlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules (hence it is a type III hypersensitivity reaction). The activation of the alternative complement pathway results in the deposition of IgA aggregates or IgA complexes in target organs (with deposition of C3). […] This leads to the production of inflammatory mediators, including vascular prostaglandins like prostacyclin, which may play a key role in the development of IgAV and its organ-specific clinical manifestations. […] The genetic basis remains unclear except for involvement of the human leukocyte antigen region of the genome. […] It is hypothesized to involve autoimmunity triggered by infections. Streptococcus strains and Parainfluenza virus are the most commonly associated pathogens, and in children Human Parvovirus B19 is a frequent viral trigger.

• #27 Henoch-Schönlein Purpura: A Literature Review | HTML | Acta Dermato-Venereologica

  https://www.medicaljournals.se/acta/content/html/10.2340/00015555-2733

  Henoch-Schnlein purpura is the most common childhood vasculitis, but may also affect adults. The clinical manifestations are thought to arise from IgA depositions in blood vessel walls in the affected organs, mostly skin, gastrointestinal tract, joints and kidneys. The pathophysiology behind HSP is not yet completely understood. The interaction between leukocytes and vascular endothelial cells contributes to the pathogenesis of HSP. Endothelial damage, perivascular leukocytic infiltrates, chemokines and cytokines are important factors in this process. Vascular deposition of IgA1-containing immune complexes plays a pathogenic role. Complement activation, cellular damaging and IgA deposition suggest that HSP is an IgA-mediated dysregulated immune response to an antigen. Through binding and activation of complement factors, IgA cross-reacts with endothelial cells and damages the cells. In HSP, the dysregulated immune response may result in inflammation and vasculitis without a granulomatous reaction. Several antibodies, cytokines, chemokines, receptors, and transmembrane proteins have been found to be involved. Amongst these are cytokines, such as tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-8. Studies showed that Toll-like receptors TLR-2 and TLR-4 were upregulated in children with HSP. One study stated that plasma levels of IgA anti-beta2-glycoprotein I antibodies are increased in childhood HSP. They are thought to have a strong association with heavy proteinuria and joint manifestations. […] The majority of cases are preceded by an upper respiratory infection, and patients show vascular depositions of IgA immune complexes in several organ systems, which lead to the disease manifestations.

• #28 Henoch scholein purpura | PPT

  https://www.slideshare.net/slideshow/henoch-scholein-purpura/127385550

  Henoch-Schnlein purpura (HSP) is an acute immunoglobulin A (IgA)-mediated disorder characterized by a generalized vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS). […] The characteristic pathological feature of HSP vasculitis is a deposition of IgA-containing immune complexes in the vessel walls of affected organs and the kidney mesangium. […] Deposited immune complexes activate the alternative complement pathway (with deposition of C3) and recruit inflammatory cells causing glomerulonephritis. […] Deposition of IgA1-containing immune complexes in other sites (skin, gut, joints) leads to organ-specific clinical manifestations of HSP. […] Henoch-Schnlein purpura (HSP) is a systemic vasculitis with multiorgan involvement. The classic tetrad of signs and symptoms includes: 1/ Palpable purpura 2/ Arthritis or arthralgia 3/ Abdominal pain 4/ Renal disease. […] The most commonly implicated respiratory pathogens include: Streptococcus, Staphylococcus, Parainfluenza. […] The majority of HSP cases are preceded by an upper respiratory tract infection suggesting a potential infectious trigger.

• #29 Henoch scholein purpura | PPT

  https://www.slideshare.net/slideshow/henoch-scholein-purpura/127385550

  Henoch-Schnlein purpura (HSP) is an acute immunoglobulin A (IgA)-mediated disorder characterized by a generalized vasculitis involving the small vessels of the skin, the gastrointestinal (GI) tract, the kidneys, the joints, and, rarely, the lungs and the central nervous system (CNS). […] The characteristic pathological feature of HSP vasculitis is a deposition of IgA-containing immune complexes in the vessel walls of affected organs and the kidney mesangium. […] Deposited immune complexes activate the alternative complement pathway (with deposition of C3) and recruit inflammatory cells causing glomerulonephritis. […] Deposition of IgA1-containing immune complexes in other sites (skin, gut, joints) leads to organ-specific clinical manifestations of HSP. […] Henoch-Schnlein purpura (HSP) is a systemic vasculitis with multiorgan involvement. The classic tetrad of signs and symptoms includes: 1/ Palpable purpura 2/ Arthritis or arthralgia 3/ Abdominal pain 4/ Renal disease. […] The most commonly implicated respiratory pathogens include: Streptococcus, Staphylococcus, Parainfluenza. […] The majority of HSP cases are preceded by an upper respiratory tract infection suggesting a potential infectious trigger.

• #30 IgA Nephropathy and Henoch-Schönlein Purpura | Propath

  https://www.propath.com/diagnostic-services/resources/iga-nephropathy-and-henoch-schoenlein-purpura/

  It has been suggested that some IgA1 molecules produced by immunoglobulin-secreting cells in patients with IgA nephropathy are galactose-deficient and are recognized by anti-glycan IgG (or IgA1) antibodies. The IgA1 containing immune complexes escape normal clearance mechanisms, reach the renal circulation, pass through the fenestrae in the glomerular capillaries overlying the mesangium, bind to mesangial cells and induce glomerular injury. IgA nephropathy would, therefore, be classified as an autoimmune disease with the aberrantly glycosylated IgA1 acting as the autoantigen.

• #31 Henoch-Schönlein purpura pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Henoch-Sch%C3%B6nlein_purpura_pathophysiology

  It has been reported that in patients with HSP, the activity of 1,3-galactosyltransferase in peripheral B cells is reduced, leading to a lack of terminal 1,3-galactosyl residues in the hinge region of IgA1. […] These aberrantly glycosylated IgA1 molecules have been shown to form immune complexes with IgG antibodies specific for galactose-deficient IgA1, thereby inhibiting the binding of the IgA molecules to hepatic receptors and avoiding their internalization and degradation by hepatic cells. […] The complexes may then deposit in renal mesangial areas and activate the complement system by the alternative or lectin pathways, which play a major role in the pathophysiology of this disease. […] Further, after depositing in the mesangium, the galactose-deficient IgA1 immune complexes activate mesangial cells.

• #32 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  Activation of the alternative and lectin pathways of the complement system by the Gd-IgA1 ICs also plays a relevant role. Elevated deposits of complement components such as C3a, C5a, C4, and the membrane attack complex (C5b-9) are found in IgAV patients, and their presence correlates with disease severity, especially in cases involving renal complications. […] The activation of T-cells and B-cells is also relevant. […] Environmental triggers may promote the development of the IgAV. Mucosal infections often precede IgAV onset, and several pathogens have been implicated in triggering the disease, such as viruses (Hepatitis B or parvovirus) or bacteria, among which Streptococcus, Staphylococcus or Helicobacter pylori stand out. […] Genetic susceptibility has been described in patients with IgAV.

• #33 The role of T cells in the development of Henoch-Schonlein purpura

  https://www.imrpress.com/journal/fbl/23/5/10.2741/4619

  Henoch-Schonlein purpura (HSP) is an IgA-mediated disorder that most commonly occurs in children. Its etiology and pathogenesis remain unknown. […] In recent years, numerous studies have pointed to a dysfunction of T cells in the pathogenesis of HSP. Here, we will review the epidemiology, clinical and molecular characteristics of HSP, as well as abnormalities of Th cell subsets in this disorder. Finally, we will discuss the key factors that are involved in Th cell differentiation as potential novel targets for the prevention and treatment of HSP.

• #34 Association between allergic diseases and risks of HSP and HSP nephritis: a population-based study | Pediatric Research

  https://www.nature.com/articles/pr2015271

  Some allergic inflammation-associated mediators have been reported in acute stage of Henoch-Schnlein purpura (HSP). However, the association of children with allergic diseases and their subsequent risks of HSP and HSP nephritis remain unknown. […] The exact etiology and pathogenesis of HSP are unknown. However, HSP is regarded as a specific immune-mediated inflammation induced by environmental factors, such as infections and seasonal variation. […] Some inflammatory mediators, including tumor necrosis factor (TNF)-, interleukin-6, IL-8, transforming growth factor (TGF)-, vascular endothelial growth factor (VEGF), and cysteinyl leukotrienes, have been reported to be higher in children with acute HSP than in healthy controls. […] Elevated Th2-mediated biological markers such as elevated serum IgE, serum eosinophil cationic protein (ECP), and urinary leukotriene E4 levels were found in acute stage of HSP.

• #35 Association between allergic diseases and risks of HSP and HSP nephritis: a population-based study | Pediatric Research

  https://www.nature.com/articles/pr2015271

  The complexity of Th1/Th2 interaction of HSP raises a research interest whether Th2-mediated allergic diseases have any influence on the development of HSP and HSP nephritis. […] This population-based study suggests that children with allergic diseases, including allergic conjunctivitis, AR, asthma, and atopic dermatitis, were more likely to develop HSP regardless of sex, age, and season. […] HSP is a systemic form of small-vessel vasculitis characterized by elevated serum IgA levels, vascular deposition of IgA-contained immune complexes, and increased proinflammatory cytokines during the acute stage. […] HSP was originally considered a Th1-mediated systemic form of vasculitis with a cytokine cascade and small-vessel endothelial cell lesions in the acute stage. […] In contrast, increasing numbers of studies have revealed elevated levels of Th2-related biomarkers in children with HSP.

• #36 Pathogenesis of IgA Vasculitis: An Up-To-Date Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8630619/

  The hallmark histologic feature of IgAV is leukocytoclastic vasculitis with IgA immune complex deposits in small vessels. […] Gd-IgA1-dominant IgA deposits were detected in the kidney, skin, and gastrointestinal tract biopsies, and it was considered an important factor in the immunopathogenesis of IgAV. […] The formation of the Gd-IgA1 immune complex is a critical step in the pathogenesis of IgAV. […] The proliferation of mesangial cells can be stimulated by Gd-IgA1 immune complexes, but not isolated Gd-IgA1. […] The serum level of Gd-IgA1 is not correlated with the intensity of Gd-IgA1 deposits in the kidney and skin, suggesting that factors other than size and amount of CIC influence the deposition of immune complexes and other mechanisms are involved in the deposition of Gd-IgA1.

• #37 Pathogenesis of IgA Vasculitis: An Up-To-Date Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8630619/

  The hallmark histologic feature of IgAV is leukocytoclastic vasculitis with IgA immune complex deposits in small vessels. […] Gd-IgA1-dominant IgA deposits were detected in the kidney, skin, and gastrointestinal tract biopsies, and it was considered an important factor in the immunopathogenesis of IgAV. […] The formation of the Gd-IgA1 immune complex is a critical step in the pathogenesis of IgAV. […] The proliferation of mesangial cells can be stimulated by Gd-IgA1 immune complexes, but not isolated Gd-IgA1. […] The serum level of Gd-IgA1 is not correlated with the intensity of Gd-IgA1 deposits in the kidney and skin, suggesting that factors other than size and amount of CIC influence the deposition of immune complexes and other mechanisms are involved in the deposition of Gd-IgA1.

• #38 IgA Vasculitis (Henoch-Schonlein Purpura): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/984105-overview

  The predominance of IgA1 in IgAV may be a consequence of abnormal glycosylation of O-linked oligosaccharides unique to the IgA1 hinge region. Patients with IgAV and IgA nephritis express inherited galactose-deficient glycosylation of IgA1 molecules. […] IgAV-associated nephritis is characterized by an abnormal IgA1 glycosylation pattern with reduced galactosylation. […] The hinge region of IgA1 contains up to six major glycosylation sites at serine and threonine residues. The O-glycans include a core N-acetylgalactosamine (GalNAc), which is usually extended with galactose to form Gal1,3GalNAc, which can bind to N-acetylneuraminic acid (Neu5Ac). Thus, each IgA1 O-glycan can have one of four short carbohydrate structures (types III, IV, V, and VI), leading to a mixture of IgA1 forms with varying degrees of galactosylation.

• #39 Henoch-Schönlein purpura pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Henoch-Sch%C3%B6nlein_purpura_pathophysiology

  This results in the proliferation of cells such as macrophages and lymphocytes and the production of inflammatory and profibrogenic cytokines and chemokines, which play a pivotal role in mesangial cell proliferation, matrix expansion, and inflammatory cell recruitment. […] Activation of the eosinophils and expression of the alpha-smooth muscle actin in the kidney also play a vital role in the pathogenesis of Henoch-Schnlein purpura.

• #40 IgA Vasculitis (Henoch-Schönlein Purpura) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537252/

  IgA vasculitis, formerly known as Henoch-Schnlein purpura, is a complex immune-mediated vasculitis characterized by the involvement of small blood vessels in various organ systems. […] The pathophysiology of IgA vasculitis is not fully understood; however, IgA plays a significant role. Mucous membranes of the salivary glands, lungs, and gastrointestinal tract produce IgA. Plasma B-cells produce other classes of immunoglobulins (IgG, IgE, IgM). IgA1 is implicated in IgaV (rather than the IgA2 subtype) and is associated with abnormally low galactose levels. […] IgA-antibody immune complexes are formed in response to antigenic exposure from an infection or medication. They are then deposited in the small vessels (usually capillaries) of the skin, joints, kidneys, and gastrointestinal tract. This results in an influx of inflammatory mediators such as prostaglandins. The complement system can also be activated when C3-receptor lymphocytes bind to immune complexes and deposit in the vessel walls, contributing to the hyper-inflammatory response. If the immune complexes are deposited in the intestinal wall, they may cause gastrointestinal hemorrhage. […] Immune complexes deposited in the skin cause palpable purpura and petechiae.

• #41 Henoch-Schönlein Purpura (HSP): Symptoms and Treatment

  https://patient.info/allergies-blood-immune/henoch-schonlein-purpura-leaflet

  In around half of people with Henoch-Schönlein purpura, the kidneys become affected. If immune complexes are deposited in the kidneys, this can lead to inflammation of the kidneys, known as nephritis. This complication usually develops within one month after the rash starts but can sometimes develop up to six months afterwards. In most people, kidney involvement will get better on its own. However, in some people, a more persistent and serious nephritis can develop. […] About three in ten people with HSP develop this bleeding in the gut. If immune complexes are deposited in the blood vessels of the wall of the gut (intestine), this can cause bleeding within the gut (gastrointestinal bleeding). This can lead to symptoms such as passing blood in the stools (faeces). Rarely, bleeding in the gut can be severe and life-threatening.

• #42 IgA Vasculitis (Henoch-Schönlein Purpura) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537252/

  IgA vasculitis, formerly known as Henoch-Schnlein purpura, is a complex immune-mediated vasculitis characterized by the involvement of small blood vessels in various organ systems. […] The pathophysiology of IgA vasculitis is not fully understood; however, IgA plays a significant role. Mucous membranes of the salivary glands, lungs, and gastrointestinal tract produce IgA. Plasma B-cells produce other classes of immunoglobulins (IgG, IgE, IgM). IgA1 is implicated in IgaV (rather than the IgA2 subtype) and is associated with abnormally low galactose levels. […] IgA-antibody immune complexes are formed in response to antigenic exposure from an infection or medication. They are then deposited in the small vessels (usually capillaries) of the skin, joints, kidneys, and gastrointestinal tract. This results in an influx of inflammatory mediators such as prostaglandins. The complement system can also be activated when C3-receptor lymphocytes bind to immune complexes and deposit in the vessel walls, contributing to the hyper-inflammatory response. If the immune complexes are deposited in the intestinal wall, they may cause gastrointestinal hemorrhage. […] Immune complexes deposited in the skin cause palpable purpura and petechiae.

• #43 Delayed diagnosis of abdominal Henoch-Schonlein purpura in children: A case report

  https://www.wjgnet.com/2307-8960/full/v11/i26/6311.htm

  Henoch-Schonlein purpura (HSP) is one of the most common vasculitis in childhood. The main pathogenesis is leukocytoclastic vasculitis and deposition of immunoglobulin A (IgA) immune complexes in small blood vessels. HSP can affect the skin, joints, gastrointestinal tract, and kidney, with skin purpura as the initial symptom in most cases. Abdominal pain is a common symptom of HSP, mostly manifesting after rash. […] Abdominal pain is a common symptom of HSP that presents mostly after the rash and rarely precedes it. Here, we highlighted an unusual case of a pediatric HSP patient with purpuric rash emerging after 19 d of persistent abdominal pain. […] HSP, also called immunoglobulin A vasculitis, characterized by generalized aseptic inflammation of small blood vessels as a pathological basis, is the most common vasculitis in childhood. The main clinical manifestations include skin purpura, abdominal pain and gastrointestinal hemorrhage, joint swelling and pain, and renal involvement. Rash and abdominal pain are the most common symptoms. Gastrointestinal symptoms, reported in 50%85% of HSP patients, are possibly attributed as secondary to edema and hemorrhage in the gastrointestinal wall and mesentery, and include nausea and vomiting, vomiting of blood, and bloody stools.

• #44 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  The pathophysiology of IgAV is multifactorial, and involves complex interactions between the immune system, genetic predisposition, and environmental triggers. A hallmark of IgAV is the deposition of IgA1-dominant ICs in small vessels, which causes inflammation in the skin, kidneys, joints, and GI tract. […] One of them is an aberrant glycosylation of IgA1. In this regard, IgA1, which is one of the subclasses of IgA, is glycosylated at its hinge region through a process called O-glycosylation. In IgAV, defective glycosylation results in the formation of Gd-IgA1, which predisposes individuals to the production and deposition of pathogenic IC. […] Gd-IgA1 interaction with autoantibodies (either IgA1 or IgG antibodies) leads to the formation of circulating IC. These Gd-IgA1 ICs then deposit in small vessel walls of the skin, kidneys, or GI tract, causing localized inflammation.

• #45 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  The pathophysiology of IgAV is multifactorial, and involves complex interactions between the immune system, genetic predisposition, and environmental triggers. A hallmark of IgAV is the deposition of IgA1-dominant ICs in small vessels, which causes inflammation in the skin, kidneys, joints, and GI tract. […] One of them is an aberrant glycosylation of IgA1. In this regard, IgA1, which is one of the subclasses of IgA, is glycosylated at its hinge region through a process called O-glycosylation. In IgAV, defective glycosylation results in the formation of Gd-IgA1, which predisposes individuals to the production and deposition of pathogenic IC. […] Gd-IgA1 interaction with autoantibodies (either IgA1 or IgG antibodies) leads to the formation of circulating IC. These Gd-IgA1 ICs then deposit in small vessel walls of the skin, kidneys, or GI tract, causing localized inflammation.

• #46 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  The pathophysiology of IgAV is multifactorial, and involves complex interactions between the immune system, genetic predisposition, and environmental triggers. A hallmark of IgAV is the deposition of IgA1-dominant ICs in small vessels, which causes inflammation in the skin, kidneys, joints, and GI tract. […] One of them is an aberrant glycosylation of IgA1. In this regard, IgA1, which is one of the subclasses of IgA, is glycosylated at its hinge region through a process called O-glycosylation. In IgAV, defective glycosylation results in the formation of Gd-IgA1, which predisposes individuals to the production and deposition of pathogenic IC. […] Gd-IgA1 interaction with autoantibodies (either IgA1 or IgG antibodies) leads to the formation of circulating IC. These Gd-IgA1 ICs then deposit in small vessel walls of the skin, kidneys, or GI tract, causing localized inflammation.

• #47 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  Activation of the alternative and lectin pathways of the complement system by the Gd-IgA1 ICs also plays a relevant role. Elevated deposits of complement components such as C3a, C5a, C4, and the membrane attack complex (C5b-9) are found in IgAV patients, and their presence correlates with disease severity, especially in cases involving renal complications. […] The activation of T-cells and B-cells is also relevant. […] Environmental triggers may promote the development of the IgAV. Mucosal infections often precede IgAV onset, and several pathogens have been implicated in triggering the disease, such as viruses (Hepatitis B or parvovirus) or bacteria, among which Streptococcus, Staphylococcus or Helicobacter pylori stand out. […] Genetic susceptibility has been described in patients with IgAV.

• #48 Henoch-Schönlein Purpura (HSP) | Doctor

  https://patient.info/doctor/henoch-schonlein-purpura-pro

  Henoch-Schnlein purpura (HSP) is an IgA-mediated, autoimmune hypersensitivity vasculitis of childhood. The aetiology remains unknown. […] The cause is unknown, but a mix of genetic, immune and environmental factors appear to be involved. […] IgA immune complexes are involved in the pathophysiology of HSP, depositing in the small blood vessels of the skin, joints, kidneys and gastrointestinal tract, causing an inflammatory reaction. […] The long-term prognosis of HSP is directly dependent on the severity of renal involvement.

• #49 IgA Vasculitis (Henoch–Schönlein Purpura): An Update on Treatment

  https://www.mdpi.com/2077-0383/13/21/6621

  In summary, the pathophysiology of IgAV involves a combination of genetic predisposition, environmental factors, in particular infections, and immune dysregulation, with Gd-IgA1 and ICs formation playing a central role. The deposition of these complexes in small vessels triggers a local inflammatory response, involving both complement activation and the recruitment of immune cells, leading to the characteristic clinical features of the disease.

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