Regulatory T cell/Th17 balance in the pathogenesis of paediatric Behçet disease

Filleron, Anne; Tran, Tú-Anh; Hubert, Audrey; Letierce, Alexia; Churlaud, Guillaume; Koné‐Paut, Isabelle; Saadoun, David; Cezar, Renaud; Corbeau, Pierre; Rosenzwajg, Michelle

doi:10.1093/rheumatology/keab253

Cited by 22 publications

(13 citation statements)

References 28 publications

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“…The frequency of circulating Th17 cells and serum levels of IL-17A are increased in BD compared with healthy controls and are correlated with disease activity. Circulating Treg proportion is decreased in BD and the Th17/Treg ratio is higher in BD patients compared with controls ( 150 – 153 ). The Th17 and Th1 hyperactivation observed in BD is partially mediated by a decreased in B and T lymphocyte attenuator (BTLA) expression ( 154 ).…”

Section: Role Of the Th17 Pathway In Vasculitismentioning

confidence: 99%

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

2022

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The involvement of IL-17A in autoimmune and inflammatory diseases has prompted the development of therapeutic strategies to block the Th17 pathway. Promising results came from their use in psoriasis and in ankylosing spondylitis. IL-17A acts on various cell types and has both local and systemic effects. Considering the premature mortality observed during chronic inflammatory diseases, IL-17A action on vascular cells was studied. Both in vitro and in vivo results suggest that this cytokine favors inflammation, coagulation and thrombosis and promotes the occurrence of cardiovascular events. These observations led to study the role of IL-17A in diseases characterized by vascular inflammation, namely allograft rejection and vasculitis. Increased circulating levels of IL-17A and histological staining reveal that the Th17 pathway is involved in the pathogenesis of these diseases. Vasculitis treatment faces challenges while the use of steroids has many side effects. Regarding results obtained in giant cell arteritis with IL-6 inhibitors, a cytokine involved in Th17 differentiation, the use of anti-IL-17 is a promising strategy. However, lessons from rheumatoid arthritis and multiple sclerosis must be learnt before targeting IL-17 in vasculitis, which may be culprit, consort or both of them.

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Section: Role Of the Th17 Pathway In Vasculitismentioning

confidence: 99%

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

2022

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“…16S rRNA metagenomic analysis was performed in the feces to determine the differences in the composition of the microbial population between normal and BS mice. The orientation of T cell subpopulations in paediatric BS was explored, focusing on regulatory T lymphocyte (Treg)/Th17 imbalance (14). A bias towards Th17 polarisation in active and remitting BS was observed.…”

Section: Immunopathogenesismentioning

confidence: 99%

Behçet's syndrome: one year in review 2022

Hatemi

Seyahi

Fresko

et al. 2022

Clinical and Experimental Rheumatology

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This review highlights publications on different aspects of Behçet's syndrome (BS) that appeared in 2021 and provides a critical view. These publications include works on the epidemiology of BS across different continents, newly developed instruments to assess damage in BS, studies highlighting the immunopathogenesis, genetics and epigenetic factors, histopathology of the pathergy lesion, clinical and imaging aspects of vascular involvement, and safety and efficacy of therapeutic agents including tocilizumab, apremilast and direct oral anticoagulants.

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“…HLA-B51 is known to be the strongest genetic risk factor, correlating with a higher prevalence of genital ulcers and ocular and skin manifestations, but with a lower gastrointestinal (GI) involvement [ 13 , 14 ]. A recent study in the pediatric population found an overexpression of Th17 lymphocytes linked to a functional inability of regulatory T cells to counterbalance the Th17 response during flares [ 15 ]. This finding is also supported by genome-wide association studies that have identified a link with a variant located in close proximity to the gene encoding the interleukin (IL)-23 receptor, a major inducer of Th17 differentiation [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment Options in Pediatric Behçet’s Disease

2023

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Behçet’s disease is a rare and poorly understood vasculitis affecting blood vessels of all types and sizes. Uveitis and oral and genital ulcers represent the typical clinical triad. Populations along the ancient trading route connecting the Mediterranean basin with the Middle and Far East are most affected. Up to a quarter of the cases has a pediatric onset, typically around puberty. The aim of the treatment is early intervention to control inflammation, with symptom relief and prevention of relapses, damage, and complications. The heterogeneous clinical presentation often requires a multidisciplinary and tailored approach. Ocular, neurological, gastrointestinal, and vascular involvement is associated with a worse prognosis and needs more aggressive treatments. In young patients with expected prolonged disease, treatment should also focus on preventive measures and lifestyle advice. In recent years, the pharmacological armamentarium has grown progressively, although only a limited number of drugs are currently authorized for pediatric use. Most evidence for these drugs still derives from adult studies and experience; these are prescribed as off-label medications and are only available as adult formulations. Corticosteroids frequently represent the mainstay for the management of the initial acute phases, but their potential serious adverse effects limit their use to short periods. Different conventional disease-modifying anti-rheumatic drugs have long been used. Many other biologic drugs targeting different cytokines such as interleukin-1, interleukin-6, and interleukin-17 and treatments with small molecules including the phosphodiesterase 4 and Janus kinase inhibitors are emerging as novel promising therapeutic agents. In recent years, a growing interest has developed around anti-tumor necrosis factor agents that have often proven to be effective in severe cases, especially in those with a gastrointestinal and ocular involvement.

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Regulatory T cell/Th17 balance in the pathogenesis of paediatric Behçet disease

Cited by 22 publications

References 28 publications

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

The Th17 Pathway in Vascular Inflammation: Culprit or Consort?

Behçet's syndrome: one year in review 2022

Treatment Options in Pediatric Behçet’s Disease

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