Takayasu arteritis: a geographically distant but immunologically proximal MHC-I-opathy

IF 15 1区医学 Q1 RHEUMATOLOGY

Lancet Rheumatology Pub Date : 2025-01-21 DOI:10.1016/S2665-9913(24)00307-2

Kerem Abacar MD , Tom Macleod PhD , Prof Haner Direskeneli MD , Prof Dennis McGonagle FRCPI PhD

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引用次数: 0

Abstract

Takayasu arteritis, a granulomatosis vasculitis with a pathogenesis that is poorly defined but known to be associated with HLA-B*52, shares many features with other MHC-I-opathies. In addition to the shared clinical features of inflammatory bowel diseases, cutaneous inflammation, and HLA-B*52, is shared association of an IL12B single- nucleotide polymorphism encoding the common IL-12 and IL-23 p40 subunit, which might affect not only type 17 cytokine responses, but also IFNγ and TNF production—the cardinal type 1 cytokines in granuloma formation. Considering the translational context of responses to TNF inhibition in Takayasu arteritis, in this Personal View we propose Takayasu arteritis as a type 1 MHC-I-opathy. Additionally, type 1 and type 17 T-cell immune responses show immune plasticity, which connects the overlapping features of Takayasu arteritis and spondyloarthritis spectrum disorders, providing a basis for shared anti-TNF responses, and points to p40 and IFNγ cytokine antagonism and potential selective CD8 T-cell repertoire ablation.

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高须动脉炎：地理上远处但免疫学上近端mhc - i病变。

Takayasu动脉炎是一种肉芽肿性血管炎，其发病机制尚不明确，但已知与HLA-B*52有关，与其他mhc - i病变有许多共同特征。除了炎症性肠病、皮肤炎症和HLA-B*52的共同临床特征外，IL12B单核苷酸多态性编码共同的IL-12和il - 23p40亚基，这可能不仅影响17型细胞因子的反应，还可能影响IFNγ和TNF的产生-肉芽肿形成的主要1型细胞因子。考虑到高松动脉炎对TNF抑制反应的翻译背景，在本个人观点中，我们提出高松动脉炎是一种1型mhc - i病。此外，1型和17型t细胞免疫反应表现出免疫可塑性，这与高松动脉炎和脊椎关节炎谱系障碍的重叠特征联系在一起，为共同的抗tnf反应提供了基础，并指出p40和IFNγ细胞因子拮抗和潜在的选择性CD8 t细胞库消融。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Rheumatology RHEUMATOLOGY-

CiteScore

34.70

自引率

3.10%

发文量

279

期刊介绍： The Lancet Rheumatology, an independent journal, is dedicated to publishing content relevant to rheumatology specialists worldwide. It focuses on studies that advance clinical practice, challenge existing norms, and advocate for changes in health policy. The journal covers clinical research, particularly clinical trials, expert reviews, and thought-provoking commentary on the diagnosis, classification, management, and prevention of rheumatic diseases, including arthritis, musculoskeletal disorders, connective tissue diseases, and immune system disorders. Additionally, it publishes high-quality translational studies supported by robust clinical data, prioritizing those that identify potential new therapeutic targets, advance precision medicine efforts, or directly contribute to future clinical trials. With its strong clinical orientation, The Lancet Rheumatology serves as an independent voice for the rheumatology community, advocating strongly for the enhancement of patients' lives affected by rheumatic diseases worldwide.