Immunopathogenesis of Behçet's disease

Al-Obeidi, Arshed; Nowatzky, Johannes

doi:10.1016/j.clim.2023.109661

Cited by 6 publications

(3 citation statements)

References 70 publications

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“…Among thousands of HLA class I alleles identified, only a few are linked to certain diseases, including HLA-B*51 for BD, HLA-B27 for the spondylarthritis family (ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, arthritis associated with inflammatory bowel disease (IBD)), HLA-C06:02 for psoriasis, and HLA-A29:02 for birdshot chorioretinopathy. This highlights the significance of the HLA system in immune response and disease susceptibility [47][48][49][50].…”

Section: Hla Class I Association In Antigen Presentation Tcr Antigen ...mentioning

confidence: 87%

Behçet’s Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade

Khoshbakht,

Başkurt,

Vural

et al. 2023

IJMS

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Behçet’s disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD’s pathogenesis, focusing on established genetic factors. Studies reveal that HLA-B*51 is the primary genetic risk factor, but non-HLA genes (ERAP1, IL-10, IL23R/IL-12RB2), as well as innate immunity genes (FUT2, MICA, TLRs), also contribute. Genome-wide studies emphasize the significance of ERAP1 and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between HLA-B*51 and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD’s complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.

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Section: Hla Class I Association In Antigen Presentation Tcr Antigen ...mentioning

confidence: 87%

Behçet’s Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade

Khoshbakht,

Başkurt,

Vural

et al. 2023

IJMS

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“…CD4 + effector T cells include inflammatory T helper cells, such as Th1, Th2, and Th17 cells, and regulatory T cells, T follicular helper cells, and memory T cells [21]. Previous studies have shown that activated CD4 + effector T cells and the inflammatory cytokines they produce promote the onset of BS [22]. Shimizu et al reported that when cultured with Th0-, Th1-, Th2-, and Th17-related cytokines and antibodies, naïve CD4 + T cells can upregulate genes related to these Th cells [23], indicating that increased inflammatory cytokines may promote naïve Th cell differentiation into activated effector T cells.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of peripheral CLA+ Tregs and clinical relevance in Behcet’s syndrome

Li,

Sun,

Zhu

et al. 2024

Arthritis Res Ther

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Background Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. Methods We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. Results The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants. Conclusion CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.

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“…1 ). This increased interest can be traced back to the discovery in 2000 of clonally aggregated T cells in the anterior chamber of BD patients [ 111 , 112 ]. The importance of T cell-mediated immune imbalances in BU has been underscored by recent transcriptome analyses conducted on iris samples.…”

Section: Etiology and Pathogenesismentioning

confidence: 99%

Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

Guan,

Li,

et al. 2024

J Neuroinflammation

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Behcet’s disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet’s uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients.

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Immunopathogenesis of Behçet's disease

Cited by 6 publications

References 70 publications

Behçet’s Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade

Behçet’s Disease: A Comprehensive Review on the Role of HLA-B*51, Antigen Presentation, and Inflammatory Cascade

Deficiency of peripheral CLA+ Tregs and clinical relevance in Behcet’s syndrome

Decoding Behcet’s Uveitis: an In-depth review of pathogenesis and therapeutic advances

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