Crosstalk between B cells and neutrophils in rheumatoid arthritis.
Crosstalk between B cells and neutrophils in rheumatoid arthritis.
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DOI：
10.1111/imm.13412
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发表时间：
2021-12
期刊：
影响因子：
6.4
通讯作者：
Vermeren S
中科院分区：
文献类型：
--
作者：
Karmakar U;Vermeren S
风湿性关节炎（RA）是一种慢性全身性自身免疫性疾病，主要影响滑膜关节，目前尚无治愈方法。RA的患病率约占全球人口的1%。B细胞和嗜中性粒细胞这两种关键免疫细胞之间的恶性循环发展并促进疾病。针对一系列瓜氨酸化表位的致病性抗瓜氨酸化蛋白抗体（ACPA）在RA患者的血浆和滑液中均很丰富。除了刺激多种细胞类型，ACPA和其他自身抗体，特别是类风湿因子，形成免疫复合物（IC），有效地激活中性粒细胞。中性粒细胞被大量的趋化因子附着在滑膜上，被IC局部刺激。它们产生细胞因子并释放细胞毒性化合物，包括中性粒细胞胞外陷阱（NET）、瓜氨酸化组蛋白修饰的去致密染色质链和颗粒源性中性粒细胞蛋白，这些蛋白在滑液中特别丰富。通过这种方式，中性粒细胞产生瓜氨酸化表位并释放肽基精氨酸脱亚胺酶（PAD）酶，该酶能够瓜氨酸化风湿关节中的细胞外蛋白，有助于ACPA的再生。这篇综述文章的重点是瓜氨酸的中心功能，瓜氨酸是RA中精氨酸残基的翻译后修饰。讨论内容包括ACPA和相关自身抗体、自身反应性B细胞介导的体细胞超突变逃避阴性选择、遗传和生活方式易感因素促进瓜氨酸化抗原的优势以及RA中产生ACPA的致病性B细胞和产生NET的中性粒细胞之间的恶性循环。本文综述了血清阳性类风湿关节炎中B细胞和中性粒细胞之间的相互作用及其发病机制。
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease without known cure that primarily affects synovial joints. RA has a prevalence of approximately 1% of the population worldwide. A vicious circle between two critical immune cell types, B cells and neutrophils, develops and promotes disease. Pathogenic anti‐citrullinated protein antibodies (ACPA) directed against a range of citrullinated epitopes are abundant in both plasma and synovial fluid of RA patients. In addition to stimulating numerous cell types, ACPA and other autoantibodies, notably rheumatoid factor, form immune complexes (ICs) that potently activate neutrophils. Attracted to the synovium by abundant chemokines, neutrophils are locally stimulated by ICs. They generate cytokines and release cytotoxic compounds including neutrophil extracellular traps (NETs), strands of decondensed chromatin decorated with citrullinated histones and granule‐derived neutrophil proteins, which are particularly abundant in the synovial fluid. In this way, neutrophils generate citrullinated epitopes and release peptidylarginine deiminase (PAD) enzymes capable of citrullinating extracellular proteins in the rheumatic joint, contributing to renewed ACPA generation. This review article focusses on the central function of citrullination, a post‐translational modification of arginine residues in RA. The discussion includes ACPA and related autoantibodies, somatic hypermutation‐mediated escape from negative selection by autoreactive B cells, promotion of the dominance of citrullinated antigens by genetic and lifestyle susceptibility factors and the vicious circle between ACPA‐producing pathogenic B cells and NET‐producing neutrophils in RA. This article reviews insights into cross‐talk between B cells and neutrophils in seropositive rheumatoid arthritis and its pathogenesis.
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