Materiały źródłowe

• #1 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  Behet’s syndrome (BS) can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. […] Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. […] BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders.

• #2 Behçet’s Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11051811/

  Behets disease is a systemic inflammatory disorder of unknown etiology. […] The pathogenesis of Behets disease remains mysterious, believed to result from an abnormal immune response triggered by an environmental agent in a genetically susceptible individual. […] Current evidence implicates environmental triggers eliciting aberrant innate and adaptive immune responses in genetically predisposed individuals. […] Altered neutrophil and T-cell activation, polarization of pro-inflammatory cytokines, and loss of immune tolerance are believed to drive the inflammatory cascade. […] The interplay between innate immunity and adaptive immunity could sustain the long-term inflammatory condition seen in Behets. […] The etiopathogenesis of Behets disease has evaded elucidation despite decades of research.

• #3 Behcet Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329099-overview

  Because of the degree of neutrophilic infiltration demonstrated in characteristic Behet disease lesions (eg, hypopyon, pustular lesions, and pathergy reactions), the activity and function of these cells has been explored extensively. […] Some studies have found that cytokine release in Behet disease may, by an unknown mechanism, place neutrophils in a static pre-excitatory primed state, eventually triggered into hyperactivity by environmental stimuli at a lower threshold than in individuals who do not have Behet disease. […] Behet disease is a sporadic disease, but a familial aggregation is well known. Carriers of HLA-B51/HLA-B5 have an increased risk of developing Behet disease compared with noncarriers. […] HLA-B51 is the strongest associated genetic factor and it has been shown to be more prevalent in Turkish, Middle Eastern, and Japanese populations, corresponding with a higher prevalence of Behet disease in these populations.

• #4 Behçet disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/behcet-disease/

  Behçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). […] The cause of Behçet disease is unknown. The condition probably results from a combination of genetic and environmental factors, most of which have not been identified. However, a particular variation in the HLA-B gene has been associated with the risk of developing Behçet disease. […] The HLA-B gene provides instructions for making a protein that plays an important role in the immune system. […] A variation of the HLA-B gene called HLA-B51 increases the risk of developing Behçet disease by about a factor of six, although the mechanism is not well understood. […] Other genetic and environmental factors likely contribute to the risk of Behçet disease. Researchers are studying several genes related to immune system function. It also appears likely that environmental factors, such as certain bacterial or viral infections, play a role in triggering the disease in people who are at risk. However, the influence of genetic and environmental factors on the development of this complex disorder remains unclear.

• #5 Behcet Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329099-overview

  In addition, genome-wide association (GWA) studies have linked increased susceptibility to Behet disease with polymorphisms in genes encoding for cytokines, activator factors, and chemokines. […] An allele of the IL-10 gene locus (rs 1800872 A) was found in significantly high levels in patients with Behet disease compared with a control group. This finding suggests that this allele could contribute to the genetic susceptibility for Behet disease through expression and regulation of interleukin 10 (IL-10), levels of which were also found to be significantly high in patients with the disease.

• #6 Behçet’s disease – Wikipedia

  https://en.wikipedia.org/wiki/Beh%C3%A7et%27s_disease

  The cause is not well-defined, but it is primarily characterized by auto-inflammation of the blood vessels. […] The primary mechanism of the damage is autoimmune, which by definition is an overactive immune system that targets the patient’s own body. The involvement of a subset of T cells (Th17) seems to be important. […] Research suggests that previous infections may provoke the autoimmune responses present in Behet’s disease. […] An association with the GIMAP („GTPase of the immunity-associated protein”) family of genes on the long arm of chromosome 7 (7q36.1) has been reported. […] HLA-B51 is strongly associated with Behet’s disease. […] Vasculitis resulting in occlusion of the vessels supplying the optic nerve may be the cause of acute optic neuropathy and progressive optic atrophy in Behet’s disease.

• #7 :: YMJ :: Yonsei Medical Journal

  https://eymj.org/DOIx.php?id=10.3349/ymj.2023.0578

  Genetic and environmental factors contribute to the disease onset and flare over time. In a meta-analysis, HLA-B51, MHC class I allele, was consistently associated with BD. Genome-wide association studies have revealed interleukin (IL)-10, IL-23R-IL-12RB2, IL-1A-IL-1B, CCR1, and ERAP1 as additional susceptibility genes for BD. Although microorganisms like Streptococcus sanguis and herpes simplex virus I had been implicated, no single pathogen has proved as a causative agent until now. Microbiome may contribute to the pathogenesis. […] Immunological factors were also related to the pathogenesis, resulting in tissue injury. Neutrophil hyperactivation, NK cells, Th 1 cells, and Th 17 cells are frequently suggested as a prominent immunologic abnormality. In studies of BD patients with vascular manifestations, inflammation has been linked to thrombosis. Although the pathogenesis of thrombosis is not known clearly, it is now recognized that inflammation promotes thrombosis through endothelial dysfunction, platelet hyperactivation, and increased tissue factor expression. On the other hand, coagulation components, including fibrinogen, thrombin, factor Xa, and factor VIIa, can potentially influence through specific receptors on the immune cells and amplify the inflammatory pathway. Cytokines, such as IL-1, IL-6, IL-17, tumor necrosis factor alpha (TNF), and C-X-C Motif Chemokine Ligand 8 (CXCL8), are also considered to be critical players in the pathogenesis. Recent research results have linked neutrophil hyperfunction to BD-induced inflammatory organ damage. Serum levels of CXCL8 and granulocyte colony-stimulating factor, mediators typically involved in neutrophil recruitment and activation, are usually elevated in active BD. The external release of structures containing DNA by neutrophils, namely neutrophil extracellular traps, contributes to the killing of extracellular microorganisms. This physiological process can potentially be altered and activated in BD; thus, maintaining inflammation and causing vascular damage.

• #8 Experimental Therapeutic Solutions for Behcet’s Disease | JEP

  https://www.dovepress.com/experimental-therapeutic-solutions-for-behcetrsquos-disease-peer-reviewed-fulltext-article-JEP

  In recent years, the diseases in which innate immunity and subsequently acquired immunity are activated due to impaired barrier functions in tissues in contact with environmental factors (skin, oral mucosa, and gastrointestinal system) are called MHC-1 related diseases (MHC-1-opathy). […] BD overlaps with MHC-1-opathy group diseases in many aspects. […] The antigens presented by these molecules and their mechanisms are not fully understood. […] Immune system dysregulation, altered T cell balance, and particularly the suppression of T regulatory cells activity by activation of the Th1/Th17 pathway are thought to play an essential role in the pathogenesis of BD. […] Consequently, environmental factors (S. sanguinis, etc.) or differences in salivary or gut microbiome composition can trigger innate immune system-mediated inflammation sustained by acquired or adaptive immune responses.

• #9 The roles of immune cells in Behçet’s disease | Advances in Rheumatology | Full Text

  https://advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-023-00328-w

  The interaction between HLA-B51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) in antigen-presenting cells disrupts T cell homeostasis, resulting in the down-regulation of Treg and up-regulation of Th1 and Th17. […] This dysregulation can lead to overactivation of innate immunity, ultimately manifesting as symptoms. […] A large number of studies have shown that Th1 plays a leading role in the immune pathogenesis of BD and plays a direct role in the skin and mucosal lesions of BD patients. […] The level of T cell regulator IL-12 was correlated with BD activity, suggesting that Th1 type immune response plays a pathogenic role in active disease. […] The increased proportion of Th17 cells and the decrease of Treg cells may be the related factors of BD. […] The study by Guillaume et al. suggested a significant increase in Th17 cells and a decrease in CD4+forkhead box P3(+) regulatory Tregs in the peripheral blood of BD patients.

• #10 Medical Summary of Behcet’s Disease

  https://www.behcets.com/medical-summary

  However, microsatellite data have also suggested a pathogenic role for genes located between the HLA-B and TNF regions on chromosome number 6. This region contains the MICA gene (Major Histocompatibility Complex Class I chain-related gene A), whose cell surface product is preferentially expressed on fibroblasts and endothelial cells. These gene products may have a role in the presentation of antigen to NK cells or to T cells. Analysis of triplet repeat polymorphisms of the MICA gene revealed an association of the A6 allele with Behcet’s disease in Japanese patients which is greater than that of HLA-B5.11 These findings were also demonstrated in Caucasian patients, making MICA, or a closely related gene, a leading candidate gene for the disease.

• #11 Behcet Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329099-overview

  Theories behind the pathogenesis of Behet disease currently suggest an autoimmune etiology. It is thought that in genetically predisposed individuals, exposure to an infectious agent or an environmental antigen triggers the autoimmune response. […] Exposure to an infectious agent may trigger a cross-reactive immune response. Proposed infectious agents have included the following: Herpes simplex virus (HSV), Streptococcus species, Staphylococcus species, Escherichia coli. […] The study of heat shock proteins (HSPs) has provided some insight into possible mechanisms that contribute to the development of Behet disease. Through discovery that human HSP-60 and HSP-65 share greater than 50% homology with mycobacterial HSP, enhanced T-cell response has been elicited with exposure to both bacterial and human homogenates in Behet disease patients compared with controls in United Kingdom, Japanese, and Turkish populations.

• #12 New Insights on the Pathogenesis of Behcet’s Disease

  https://www.jrd.or.kr/journal/view.html?uid=454&vmd=Full

  New Insights on the Pathogenesis of Behcet’s Disease […] Behcet’s disease (BD) is a chronic inflammatory disorder of unknown cause, characterized by recurrent oral ulcerations, genital ulcerations, ocular and skin lesions. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. […] It is noted that multiple genes, including MHC and non-MHC genes, are implicated in the pathogenesis of BD. […] Although the HLA-B51 is known to be the candidate gene showing the strongest association with BD, it is necessary to be determined whether this HLA molecule is directly involved in the pathogenesis of BD. […] Cross-reactivity between microbial 65-kD and human 60-kD heat shock proteins is demonstrated to cause an increased T cell (particularly αβ T cell) response. […] The resultant overexpression of pro-inflammatory cytokines (mainly Th-1 type) from several immune cells seems to be responsible for the enhanced inflammatory reaction, and this may be associated with the genetic factors.

• #13 Behcet Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329099-overview

  HSP-65, found in high concentrations in oral ulcers and active skin lesions in patients with Behet disease, has also been demonstrated to stimulate production of antibodies that exhibit cross-reactivity with streptococcal species present in the mouth. […] Elevated peripheral levels of gamma-delta T cells (+ T cells) in patients with Behet disease in response to exposure to mycobacterial HSPs compared with those in healthy subjects imply a role for their production. […] Systemic involvement of multiple organs is observed in Behet disease, rooted primarily in the development of vasculitic or vasculopathic lesions in the affected areas. These areas may demonstrate microscopic evidence of inflammatory tissue infiltration with both T cells and neutrophils. […] Studies of T lymphocytes have suggested a T-helper type 1 (TH1) predominant response. Both CD4+ and CD8+ lymphocytes demonstrate higher concentrations in peripheral blood, with characteristic and corresponding elevations of cytokines (interleukin [IL-2] and interferon- [IFN-]).

• #14 Streptococcal antigen in the pathogenesis of Behçet’s disease | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar988

  Patients with Behet’s disease (BD) are highly associated with HLA-B51 immunogenetically and tend to be involved with chronic infectious foci, such as tonsillitis and dental caries, by nonpathogenic streptococci in the oral cavity. […] BD patients were suggested to be hypersensitive to streptococci and we immunohistologically demonstrated the deposits of streptococcal related antigen at infiltrated cells which were adhering to the vascular walls in erythema nodosum (EN)-like lesions. […] The Japanese Research Group for BD also demonstrated that BD patients showed greater hypersensitivity against streptococcal antigens than normal healthy controls and that the BD symptoms were frequently induced by the skin tests using these antigens and the treatment of the dental caries. […] An attempt at cloning and sequencing the bes-1 gene of S. sanguis isolated from BD patients was made and it has been found that the amino acid sequence of the bes-1 gene has more than 60% of homology with the human intraocular peptide brn-3b, which is a POU domain expressed in the retinal ganglion cells.

• #15 Intestinal Behcet’s Disease: A Review of the Immune Mechanism and Present and Potential Biological Agents

  https://www.mdpi.com/1422-0067/24/9/8176

  In addition, as for intestinal BD, the location of lesions has direct contact with intestinal flora, and there may be a close relationship between gastrointestinal involvement of BD and the intestinal microbiome in theory. […] A recent study has found deviations in microbiota composition between BD patients with skin mucosa, ocular and vascular involvement. […] In the adaptive immunity of BD, cellular immunity is considered to play an important role, and T cells are the main lymphocytes, mainly Th1 cells, regulatory T cells (Tregs), and Th17 cells. […] This evidence of Th1 polarization indicated that Th1-dominant immune response has a close association with the pathogenesis of intestinal BD. […] In intestinal BD, the role of Th17 cells in the development of gastrointestinal involvement in BD is controversial.

• #16 :: YMJ :: Yonsei Medical Journal

  https://www.eymj.org/DOIx.php?id=10.3349/ymj.2016.57.1.22

  Generally, BD starts from oral ulcerations. Therefore, bacteria from normal flora of the oral mucosa have been evaluated as causative organisms. A number of Streptococcus species have been implicated. Streptococcus sanguis and its antibodies are repeatedly detected in the oral mucosa and sera of patients with BD. Streptococcus sanguis-related antigen (KTH-1) stimulates IL-6 and INF- production in patients with BD. […] In the same manner, intestinal microbiota may play an important role in IBD development. Dysbiosis of conventional microbiota, pathogenic stimulation of functionally altered commensal bacteria, host genetic defects in containing microbiota, and defective host immune regulation are generally accepted explanations of the pathogenesis of IBD. […] Close overlap of genetic variants provides considerable explanation about phenotypic and clinical similarities between intestinal BD and IBD. Despite many parallels between the two diseases, detailed distinctions regarding genetics have been steadily traced. Therefore, further studies are needed to discover the exact genetic contributions for each disease.

• #17 The roles of immune cells in Behçet’s disease | Advances in Rheumatology | Full Text

  https://advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-023-00328-w

  Behets disease (BD) is a systemic vasculitis that can affect multiple systems, including the skin, mucous membranes, joints, eyes, gastrointestinal and nervous. However, the pathogenesis of BD remains unclear, and it is believed that immune-inflammatory reactions play a crucial role in its development. […] The incidence of BD varies globally, and while its pathogenesis remains incompletely defined, the immune-inflammatory mechanism is widely considered to be the primary driver. […] Innate immunity and adaptive immune activation are recognized as crucial mechanisms in the pathogenesis of BD. […] The activation of both the innate and adaptive immune systems by various cytokines plays a crucial role in the pathogenesis and progression of BD patients. […] Immunological aberrations plays a predominant role in the pathogenesis of BD.

• #18 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  (2) Environmental etiology, including infections, microbiome, and additional triggering factors. […] (3) Immunological pathways, including neutrophils and other immune-mediated mechanisms of damage. […] The NF-B pathway is also increasingly implicated in the pathogenesis of BS. […] In this regard, it has been shown that the inflammatory features of BS might be associated with NF-B hyperactivation in immune cells. […] Neutrophils are known to play a key role in the etiopathogenesis of BS, which has traditionally been considered a neutrophilic vasculitis. […] Hyperactivated neutrophils in perivascular infiltration and tissue injury have been described in BS patients. […] These granulocytes have shown increased phagocytosis and superoxide production, potentially contributing to clot formation by fibrinogen oxidation.

• #19 The role of neutrophils in the pathogenesis of Behcet’s disease | Nurbaeva | Modern Rheumatology Journal

  https://mrj.ima-press.net/mrj/article/view/1326/0?locale=en_US

  Behcet’s disease (BD) is a systemic vasculitis of unknown etiology, characterized by damage of vessels of any type and caliber, manifested by recurrent ulcerative process in the oral cavity and genital organs, eye damage, joints, gastrointestinal tract, central nervous system and other organs involvement. The pathogenesis of the disease is complex. The contribution of both innate and adaptive immune responses is noted. A feature of BD is hyperactivation of neutrophils and neutrophilic infiltration of affected tissues. […] The review presents data from studies related to the assessment of the main functions of neutrophils in this disease. […] Possible mechanisms of neutrophil activation in Behcet’s disease. […] Neutrophil hyperchemotaxis in Behcet’s disease: a possible role for monocytes orchestrating bacterial-induced innate immune responses. […] Neutrophil activation in Behcet’s disease. […] Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behcet’s disease. […] Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease.

• #20 Behcet Disease: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/329099-overview

  Because of the degree of neutrophilic infiltration demonstrated in characteristic Behet disease lesions (eg, hypopyon, pustular lesions, and pathergy reactions), the activity and function of these cells has been explored extensively. […] Some studies have found that cytokine release in Behet disease may, by an unknown mechanism, place neutrophils in a static pre-excitatory primed state, eventually triggered into hyperactivity by environmental stimuli at a lower threshold than in individuals who do not have Behet disease. […] Behet disease is a sporadic disease, but a familial aggregation is well known. Carriers of HLA-B51/HLA-B5 have an increased risk of developing Behet disease compared with noncarriers. […] HLA-B51 is the strongest associated genetic factor and it has been shown to be more prevalent in Turkish, Middle Eastern, and Japanese populations, corresponding with a higher prevalence of Behet disease in these populations.

• #21 Vascular Behçet syndrome: from pathogenesis to treatment | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-022-00880-7

  This study investigated the pathogenesis of thrombo-inflammation in vascular Behet syndrome, and demonstrated how oxidative stress can induce pro-thrombotic modifications of fibrinogen, a key molecule involved in the coagulation pathway. […] This study showed the role of NETs as a potential mechanism of neutrophil-induced thrombo-inflammation. […] This study demonstrated how Behet syndrome is characterized by a specific microbiome signature and microbiota dysbiosis. […] This pilot study investigated for the first time the effects of tailored nutritional interventions to reduce redox status and the consequent pro-thrombotic milieu in patients with Behet syndrome. […] This study investigated for the first time the role of circulating miRNA in thrombo-inflammation in Behet syndrome.

• #22 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  Indeed, it has been recently shown that neutrophil activation promotes fibrinogen oxidation and thrombosis formation in BS. […] In addition to the role of ROS, other mechanisms implicated in typical thrombo-inflammation are also documented, including the release of neutrophil extracellular traps (NETs). […] However, considering that in BS a dense neutrophilic infiltration can be found not only at the vascular level, but also at the cutaneous, articular, ocular, intestinal, and neurological locations, it is possible to assume that neutrophils and neutrophil-derived products might also be involved in the pathogenesis of non-vascular BS involvement. […] In addition to neutrophils, natural killer (NK) cells are also known to play a role in BS. […] Therefore, overproduction of inflammatory cytokines by innate immune cells such as NK or other immune-cells (e.g., macrophages and DC) may cause a higher production of adaptive Th1- and Th17-related cytokines. […] Moreover, T cells also play a crucial role, especially CD8+ T cells, as they seem to be correlated with disease status and therefore representing a potential therapeutic target for BS. […] Understanding the pathogenesis of BS is a critical step in the development of novel and effective therapies.

• #23 :: YMJ :: Yonsei Medical Journal

  https://www.eymj.org/DOIx.php?id=10.3349/ymj.2016.57.1.22

  Although BD shows familial aggregation and a genetic background, environmental factors also contribute to triggering inflammation. Increased Th1, Th17, CD4+ and CD8+ T cell, and + T cell activities were found both in the serum or inflamed tissues of BD patients, which suggests that innate and adaptive immunity act together to initiate BD. Similar to other autoimmune disorders, BD shows Th1-type cytokine profiles. IL-2 and interferon (INF)- producing T cells were increased in patients with active BD, while IL-4 producing T cells were lower than in controls. […] The immunologic pathogenesis of IBD is summarized as exhibiting dysfunctions of the epithelial barrier, innate immune cells, and adaptive T cells. In patients with IBD, innate (macrophage, neutrophil) and acquired (T and B cell) immune responses are activated. Most pro-inflammatory cytokines involved in innate immune system are activated in both Crohn’s disease and ulcerative colitis. As in BD, Th1 and Th17 related cytokines, such as IL-12, IL-23, and IL-27, are also up-regulated in Crohn’s disease.

• #24 The roles of immune cells in Behçet’s disease | Advances in Rheumatology | Full Text

  https://advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-023-00328-w

  The interaction between HLA-B51 and endoplasmic reticulum aminopeptidase 1 (ERAP1) in antigen-presenting cells disrupts T cell homeostasis, resulting in the down-regulation of Treg and up-regulation of Th1 and Th17. […] This dysregulation can lead to overactivation of innate immunity, ultimately manifesting as symptoms. […] A large number of studies have shown that Th1 plays a leading role in the immune pathogenesis of BD and plays a direct role in the skin and mucosal lesions of BD patients. […] The level of T cell regulator IL-12 was correlated with BD activity, suggesting that Th1 type immune response plays a pathogenic role in active disease. […] The increased proportion of Th17 cells and the decrease of Treg cells may be the related factors of BD. […] The study by Guillaume et al. suggested a significant increase in Th17 cells and a decrease in CD4+forkhead box P3(+) regulatory Tregs in the peripheral blood of BD patients.

• #25 Behçet’s Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review

  https://www.mdpi.com/1648-9144/60/4/562

  Innate and adaptive immune responses are involved in immunological abnormalities, which are at the core of Behçet’s disease pathogenesis. […] Behçet’s disease may be triggered by infectious pathogens in the environment, specifically Streptococcus sanguis and herpes simplex virus. […] The interplay between innate immunity and adaptive immunity could sustain the long-term inflammatory condition seen in Behçet’s. […] Dysregulated innate and T-cell-mediated immune pathways underpin Behçet’s pathogenesis. […] Neutrophil and monocyte hyperactivity, exaggerated inflammatory cytokine responses, and Th1 skewing have been consistently demonstrated. […] More recently, Th17 cells were shown to be pathologically upregulated in active Behçet’s disease.

• #26 The roles of immune cells in Behçet’s disease | Advances in Rheumatology | Full Text

  https://advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-023-00328-w

  These cells participate in the pathogenesis of Behets disease (BD) through various differentiation phenotypes and cytokine secretion. […] The aggregation of T lymphocytes, macrophages, neutrophils, and other immune cells with high expression levels of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-) is observed in BD. […] The increased chemotaxis of neutrophils is believed to play an important role in the pathogenesis of BD, and plasma soluble factors can increase the chemotaxis of neutrophils. […] Monocytes may produce neutrophil-stimulated proinflammatory factors through TLR2 that play a role in BD. […] The lymphocyte-to-monocyte ratio (LMR), a crucial inflammatory marker, has demonstrated its ability to predict the onset, progression, and survival of certain autoimmune diseases.

• #27 Medical Summary of Behcet’s Disease

  https://www.behcets.com/medical-summary

  Interleukin-8, a chemokine responsible for neutrophilic activation, is elevated in the serum of Behcet’s patients. Elevated levels of other proinflammatory cytokines, including IL-1, IL-6, INF-, IL-12, TNF, as well as sIL-2R, have been reported in Behcet’s patients, consistent with systemic immune system activation. Mononuclear cells from these patients produce greater amounts of these cytokines ex vivo, when compared to normals. However, cytokine studies have not yet led to clinically useful measures of disease activity. […] Cytokine analysis and cellular characterization suggest a Th1 response by lymphocytes in Behcet’s disease. Other studies have shown participation of both Th1 and Th2 cells. Although circulating immune complexes and anti-endothelial antibodies have been found in Behcets patients, there is little evidence for a contribution of B cell hyperactivity in Behcet’s disease.

• #28 Behcet Syndrome: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1006358-overview

  Results of recent genome-wide association studies (GWASs) confirm the association with HLA-B51, although there is currently not a diagnostic or prognostic role for the presence of HLA-B51. These GWASs demonstrate that the most common nonHLA association is with the interleukin (IL)10 and IL23R loci and underline the essential role of the IL-10 and IL23/17 pathways in the pathogenesis of Behet syndrome. IL-6 has been shown to be elevated and IL-10 decreased in patients with Behet syndrome compared with controls, and IL-6 is elevated in those with active disease.

• #29 Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease | IntechOpen

  https://www.intechopen.com/chapters/54940

  Evidence from the GWASs further implicated several cytokines underlying the pathogenesis of BD. […] These overall observations highlight the fundamental role of cytokines as key players in the pathogenesis of BD. […] The attraction of leukocytes to tissues is essential for inflammation and is controlled by chemokines, which are chemotactic cytokines. […] The emerging evidence of a complex cytokine and chemokine network interplay involved in the pathogenesis of BD, the identification of candidate gene including cytokine polymorphisms and the proven potency of anti-cytokines treatment shed more light on the fundamental role of cytokines and chemokines in BD. […] The role of microbial triggers in BD has long been postulated since the disease was first described. […] The immunomodulatory role of vitamin D is of increasing interest, and several in vitro studies have demonstrated downregulation of inflammation by vitamin D.

• #30 Vascular Behçet syndrome: from pathogenesis to treatment | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-022-00880-7

  Behet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. […] Behet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behet syndrome. […] This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. […] Research is needed to address the contribution of epigenetic modulators in Behet syndrome thrombogenesis, to assess the diagnostic performance of vascular imaging to support Behet syndrome diagnosis, and to identify new pharmacological and non-pharmacological therapeutic approaches.

• #31 Behcet Syndrome: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1006358-overview

  Behet syndrome is characterized by recurrent aphthous ulcers, genital ulcers, and uveitis or retinal vasculitis. Other manifestations of the disease include skin lesions, arthritis, GI lesions, CNS involvement, and vascular lesions, including aneurysms and thrombosis. In Behet syndrome, the basic lesion is vasculitis. Biopsies have shown vasculitis near affected lesions, including the oral and genital ulcers and lesions of the CNS and the eyes; large vessels are affected by a vasculitis of the vasa vasorum. Vascular injuries may be superimposed on the hypercoagulability observed in some patients. […] Neutrophilic hyperfunction is observed in patients with Behet syndrome with neutrophilic infiltration of skin at the site of a prick with a sterile needle (the pathergy test). Lymphocyte function has also been reported as abnormal, with a clonal expansion of autoreactive T cells.

• #32 Behçet Disease – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/beh%C3%A7et-disease

  Behet disease is an inflammatory disorder that can include a vasculitis of small and large arteries and/or veins. Arterial and venous thrombosis may occur as well. […] The cause of Behet disease is unknown. Immunologic (including autoimmune) and viral or bacterial triggers have been suggested, and HLA-B51 is a major risk factor. […] Neutrophil infiltration is detected in biopsy specimens from oral aphthous ulcers and erythema nodosum and pathergy lesions, but no histologic changes are pathognomonic. […] Perivascular and endovascular inflammation may develop in arteries and veins. In arteries, thrombosis, aneurysm, pseudoaneurysm, hemorrhage, and stenosis can develop. […] In situ arterial or venous thromboses, aneurysms, and pseudoaneurysms are more common than stenoses and occlusions.

• #33 :: YMJ :: Yonsei Medical Journal

  https://eymj.org/DOIx.php?id=10.3349/ymj.2023.0578

  In the histology of BD, inflammatory cells are localized more around the vessels than inside the wall, unlike the histology of other systemic vasculitides. The inflammatory lesions in BD predominantly comprise infiltrating neutrophils and lymphocytes. This perivascular pattern of BD, similar to that of neutrophilic dermatosis, has been found in several organs, including mucosal ulcers, ocular lesions, and even in pulmonary aneurysms. Fibrous thickening of the vessel wall and focal aneurysmal dilatation with an overlying thrombus can often be demonstrated in the specimens of arterial disease. Medial elastic fibers are destructed and there is lymphocytic infiltration around the vasa vasorum. Inflammation of the vasa vasorum in the medial layer destroys results in elastic fibers and subsequent arterial dilatation. The pathology of venous disease comprises formation of an inflammation-induced thrombus, which is typically adherent to the inflamed vessel wall. The vessel wall is thickened due to inflammation, and it is accompanied by an organized thrombus. This is usually not complicated by thromboembolism. The typical histology of vasculitis, vessel wall infiltration by inflammatory cells, is hardly seen.

• #34 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  (2) Environmental etiology, including infections, microbiome, and additional triggering factors. […] (3) Immunological pathways, including neutrophils and other immune-mediated mechanisms of damage. […] The NF-B pathway is also increasingly implicated in the pathogenesis of BS. […] In this regard, it has been shown that the inflammatory features of BS might be associated with NF-B hyperactivation in immune cells. […] Neutrophils are known to play a key role in the etiopathogenesis of BS, which has traditionally been considered a neutrophilic vasculitis. […] Hyperactivated neutrophils in perivascular infiltration and tissue injury have been described in BS patients. […] These granulocytes have shown increased phagocytosis and superoxide production, potentially contributing to clot formation by fibrinogen oxidation.

• #35 Integrated analysis of genetic, proteinic, and metabolomic alterations in Behcet’s disease | Scientific Reports

  https://www.nature.com/articles/s41598-025-87130-4

  Numerous studies have investigated the alterations of genes, proteins, and metabolites in Behcets disease (BD). […] This study showed that the hyperactivity of Th1 and Th17 responses played an essential role in the pathogenesis of BD, and the progression of this disease was associated with enhanced neutrophil chemotaxis, vascular endothelial injury, activation of haemostatic system, and oxidative stress. […] It has been shown that BD is closely linked to T helper (Th) responses, particularly, the hyperactivity of Th1 and Th17 responses is reported to be the cornerstone of BD pathogenesis. […] Our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD. […] Overall, our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD, and pharmacotherapy that inhibits activation of the Th1/Th17-pathway axis could be a potential therapeutic target for this disease. […] Our results revealed that vascular endothelial injury is related to the pathological process of BD. […] Our results showed that hypercoagulability is closely associated with the development of BD. […] Our results showed that oxidative stress has been implicated in the progression of BD.

• #36 Vascular Behçet syndrome: from pathogenesis to treatment | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-022-00880-7

  This study investigated the pathogenesis of thrombo-inflammation in vascular Behet syndrome, and demonstrated how oxidative stress can induce pro-thrombotic modifications of fibrinogen, a key molecule involved in the coagulation pathway. […] This study showed the role of NETs as a potential mechanism of neutrophil-induced thrombo-inflammation. […] This study demonstrated how Behet syndrome is characterized by a specific microbiome signature and microbiota dysbiosis. […] This pilot study investigated for the first time the effects of tailored nutritional interventions to reduce redox status and the consequent pro-thrombotic milieu in patients with Behet syndrome. […] This study investigated for the first time the role of circulating miRNA in thrombo-inflammation in Behet syndrome.

• #37 Intestinal Behcet’s Disease: A Review of the Immune Mechanism and Present and Potential Biological Agents

  https://www.mdpi.com/1422-0067/24/9/8176

  However, the expression levels of Tregs in BD are also inconsistent based on previous studies. […] Innate immune cells are mainly composed of neutrophils, mononuclear phagocytes, dendritic cells, natural killer (NK) cells, γδ T cells, mast cells, and so on, of which abnormal activation plays an important role in the pathogenesis of BD. […] For intestinal BD, Ahn et al. revealed that extracellular high-mobility group Box 1 (HMGB1) expression, which could activate the release of cytokines and mediate inflammation in innate immunity, was significantly increased in BD patients with gastrointestinal involvement compared to BD patients without gastrointestinal involvement and healthy controls. […] Kirino et al. reported that Toll-like receptor 4 (TLR4), which mediates activation of the innate immune system, was upregulated with a reduction in the anti-inflammatory enzyme heme oxygenase (HO)-1 in peripheral blood mononuclear cells in patients with BD, suggesting the involvement of innate immunity in the pathogenesis of BD.

• #38 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  Behet’s syndrome (BS) can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. […] Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. […] BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders.

• #39 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. […] Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. […] Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. […] It is now known that the complex etiopathogenesis of BS involves more than one pathogenetic pathway, namely (1) Genetic and epigenetic factors, including geographic distribution, the association with HLA and non-HLA genes, and micro-RNA (miRNA) polymorphisms.

• #40 Etiology, Immunopathogenesis and Biomarkers in Behçet’s disease | IntechOpen

  https://www.intechopen.com/chapters/54940

  McGonagle et al. have proposed that the MHC-I-opathies share an immunopathogenetic basis including barrier dysfunction in environmentally exposed organs such as the skin and aberrant innate immune reactions at sites of mechanical stress. […] The complexity and strong LD with the HLA-B*51 allele make it difficult to explore additional independent susceptibility loci within this region. […] The advent of GWAS earlier in this century has dramatically improved our ability to identify and map successfully susceptibility loci associated with complex diseases such as BD, usually as single nucleotide polymorphisms (SNPs). […] The term cytokine was first introduced in 1974 by Cohen et al. to describe a polypeptide mediator superfamily central in the immune system generation and regulation. […] Pro-inflammatory and anti-inflammatory cytokines have been shown to be involved in patients with BD.

• #41 Integrated analysis of genetic, proteinic, and metabolomic alterations in Behcet’s disease | Scientific Reports

  https://www.nature.com/articles/s41598-025-87130-4

  Numerous studies have investigated the alterations of genes, proteins, and metabolites in Behcets disease (BD). […] This study showed that the hyperactivity of Th1 and Th17 responses played an essential role in the pathogenesis of BD, and the progression of this disease was associated with enhanced neutrophil chemotaxis, vascular endothelial injury, activation of haemostatic system, and oxidative stress. […] It has been shown that BD is closely linked to T helper (Th) responses, particularly, the hyperactivity of Th1 and Th17 responses is reported to be the cornerstone of BD pathogenesis. […] Our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD. […] Overall, our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD, and pharmacotherapy that inhibits activation of the Th1/Th17-pathway axis could be a potential therapeutic target for this disease. […] Our results revealed that vascular endothelial injury is related to the pathological process of BD. […] Our results showed that hypercoagulability is closely associated with the development of BD. […] Our results showed that oxidative stress has been implicated in the progression of BD.

• #42 Unveiling the Pathomechanism of Behçet’s Disease | EADV

  https://eadv.org/2025/02/04/unveiling-the-pathomechanism-of-behcets-disease/

  Behets disease (BD) is a chronic, relapsing multisystemic vasculitis that typically affects individuals in their 30s and 40s, leading to significant morbidity. […] the diseases pathogenesis remains enigmatic, shaped by complex genetic, environmental, autoimmune, and autoinflammatory factors. A strong association with the HLA-B*51 gene, present in 5070% of BD patients, underscores its genetic basis. […] Despite advances in understanding immune dysregulation in peripheral bloodincluding increased Th17, Th1, and cytotoxic CD8+ T cellsthe immune landscape in BDs primary site of pathology, the skin, remains poorly characterized. […] The findings underscore the central role of innate immune cells and innate T lymphocytes, along with an activated Th1/Tc1 axis, in driving BDs pathology. The studys identification of key pathways and cell types provides a foundation for targeted therapies, particularly those aimed at modulating JAK-STAT signaling or type I immune responses. […] By mapping the immune microenvironment of BD skin lesions at single-cell resolution, this research illuminates the intricate immune dysregulation underlying BD and opens new avenues for precision medicine in this challenging disease.

• #43 Vascular Behçet syndrome: from pathogenesis to treatment | Nature Reviews Rheumatology

  https://www.nature.com/articles/s41584-022-00880-7

  Behet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. […] Behet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behet syndrome. […] This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. […] Research is needed to address the contribution of epigenetic modulators in Behet syndrome thrombogenesis, to assess the diagnostic performance of vascular imaging to support Behet syndrome diagnosis, and to identify new pharmacological and non-pharmacological therapeutic approaches.

• #44 Behçet disease: Background, Treatment and More

  https://dermnetnz.org/topics/behcet-disease

  Ocular, vascular, and neurological manifestations are often more serious and require more aggressive treatment. […] Evidence of ulceration or detection of medium-vessel vasculitis on skin biopsy is an indication for systemic glucocorticoids with another immunosuppressive agent (typically azathioprine). […] Major blood vessel disease, including thrombosis is treated with immunosuppression and not anticoagulation. […] CNS involvement is typically more refractory to treatment. […] Immunopathogenesis of Behet’s disease.

• #45 Behçet Disease – Musculoskeletal and Connective Tissue Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/vasculitis/beh%C3%A7et-disease

  Central nervous system involvement is less common but is serious. Onset may be sudden or gradual. […] Behet disease has no single pathognomonic finding but may be distinguished by its combinations of relapsing symptoms with spontaneous remissions and multiple organ involvement, particularly in patients with recurrent, deep mucosal ulcers. […] Immunosuppressants, including TNF inhibitors, improve the prognosis for patients with vascular involvement.

• #46

  https://scholars.duke.edu/individual/pub1598108

  Behet’s disease (BD) is a multisystemic chronic vasculitis. Sustained and enhanced immune responses were reportedly associated with active BD. Although genetic polymorphisms increase development risk, genetic factors alone cannot account for BD development, suggesting the involvement of exogenous factors. […] In this review, we summarized the current findings on the associations of infectious agents with BD pathogenesis. The review also highlights the potential microbial risk factors and their pathogenic role in BD progression. Interactions between genetic and infectious risk factors was also discussed. Furthermore, evidence implied that after the eradication of infectious agents, BD symptoms and recurrence decreased, thus highlighting that combined use of antibiotics may be an effective therapy for BD. […] Finally, we summarized the main limitation of the current related studies, providing valuable insights and a basis for future studies on BD pathogenic factors.

• #47 Behçet’s Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11051811/

  Behets disease is a systemic inflammatory disorder of unknown etiology. […] The pathogenesis of Behets disease remains mysterious, believed to result from an abnormal immune response triggered by an environmental agent in a genetically susceptible individual. […] Current evidence implicates environmental triggers eliciting aberrant innate and adaptive immune responses in genetically predisposed individuals. […] Altered neutrophil and T-cell activation, polarization of pro-inflammatory cytokines, and loss of immune tolerance are believed to drive the inflammatory cascade. […] The interplay between innate immunity and adaptive immunity could sustain the long-term inflammatory condition seen in Behets. […] The etiopathogenesis of Behets disease has evaded elucidation despite decades of research.

• #48 Pathogenesis of Behçet syndrome – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-behcet-syndrome

  Pathogenesis of Behçet syndrome […] The etiology and pathogenesis of Behçet syndrome are discussed in this review. […] The underlying cause of Behçet syndrome is unknown. As with other autoimmune diseases, the disorder may represent aberrant immune activity triggered by exposure to an agent, perhaps infectious, in patients with a genetic predisposition to develop the disease. Both autoimmune and autoinflammatory features have been described. Major disease mechanisms in Behçet syndrome include the following: […] Genetic influences, including association with certain human leukocyte antigens (HLA) as well as some non-HLA genes.

• #49 Pathogenesis of Behçet’s Syndrome: Genetic, Environmental and Immunological Factors

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8531401/

  (2) Environmental etiology, including infections, microbiome, and additional triggering factors. […] (3) Immunological pathways, including neutrophils and other immune-mediated mechanisms of damage. […] The NF-B pathway is also increasingly implicated in the pathogenesis of BS. […] In this regard, it has been shown that the inflammatory features of BS might be associated with NF-B hyperactivation in immune cells. […] Neutrophils are known to play a key role in the etiopathogenesis of BS, which has traditionally been considered a neutrophilic vasculitis. […] Hyperactivated neutrophils in perivascular infiltration and tissue injury have been described in BS patients. […] These granulocytes have shown increased phagocytosis and superoxide production, potentially contributing to clot formation by fibrinogen oxidation.

• #50 Behcet Syndrome: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1006358-overview

  Behet syndrome is characterized by recurrent aphthous ulcers, genital ulcers, and uveitis or retinal vasculitis. Other manifestations of the disease include skin lesions, arthritis, GI lesions, CNS involvement, and vascular lesions, including aneurysms and thrombosis. In Behet syndrome, the basic lesion is vasculitis. Biopsies have shown vasculitis near affected lesions, including the oral and genital ulcers and lesions of the CNS and the eyes; large vessels are affected by a vasculitis of the vasa vasorum. Vascular injuries may be superimposed on the hypercoagulability observed in some patients. […] Neutrophilic hyperfunction is observed in patients with Behet syndrome with neutrophilic infiltration of skin at the site of a prick with a sterile needle (the pathergy test). Lymphocyte function has also been reported as abnormal, with a clonal expansion of autoreactive T cells.

• #51 Behçet’s Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review

  https://www.mdpi.com/1648-9144/60/4/562

  Innate and adaptive immune responses are involved in immunological abnormalities, which are at the core of Behçet’s disease pathogenesis. […] Behçet’s disease may be triggered by infectious pathogens in the environment, specifically Streptococcus sanguis and herpes simplex virus. […] The interplay between innate immunity and adaptive immunity could sustain the long-term inflammatory condition seen in Behçet’s. […] Dysregulated innate and T-cell-mediated immune pathways underpin Behçet’s pathogenesis. […] Neutrophil and monocyte hyperactivity, exaggerated inflammatory cytokine responses, and Th1 skewing have been consistently demonstrated. […] More recently, Th17 cells were shown to be pathologically upregulated in active Behçet’s disease.

• #52 The roles of immune cells in Behçet’s disease | Advances in Rheumatology | Full Text

  https://advancesinrheumatology.biomedcentral.com/articles/10.1186/s42358-023-00328-w

  These cells participate in the pathogenesis of Behets disease (BD) through various differentiation phenotypes and cytokine secretion. […] The aggregation of T lymphocytes, macrophages, neutrophils, and other immune cells with high expression levels of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-) is observed in BD. […] The increased chemotaxis of neutrophils is believed to play an important role in the pathogenesis of BD, and plasma soluble factors can increase the chemotaxis of neutrophils. […] Monocytes may produce neutrophil-stimulated proinflammatory factors through TLR2 that play a role in BD. […] The lymphocyte-to-monocyte ratio (LMR), a crucial inflammatory marker, has demonstrated its ability to predict the onset, progression, and survival of certain autoimmune diseases.

• #53 Integrated analysis of genetic, proteinic, and metabolomic alterations in Behcet’s disease | Scientific Reports

  https://www.nature.com/articles/s41598-025-87130-4

  Numerous studies have investigated the alterations of genes, proteins, and metabolites in Behcets disease (BD). […] This study showed that the hyperactivity of Th1 and Th17 responses played an essential role in the pathogenesis of BD, and the progression of this disease was associated with enhanced neutrophil chemotaxis, vascular endothelial injury, activation of haemostatic system, and oxidative stress. […] It has been shown that BD is closely linked to T helper (Th) responses, particularly, the hyperactivity of Th1 and Th17 responses is reported to be the cornerstone of BD pathogenesis. […] Our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD. […] Overall, our results suggest that the hyperactivity of Th1 and Th17 responses is the most prominent feature of molecular alterations in BD, and pharmacotherapy that inhibits activation of the Th1/Th17-pathway axis could be a potential therapeutic target for this disease. […] Our results revealed that vascular endothelial injury is related to the pathological process of BD. […] Our results showed that hypercoagulability is closely associated with the development of BD. […] Our results showed that oxidative stress has been implicated in the progression of BD.

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