Recent Advances in the Immunopathology of Axial Spondyloarthritis: with and without HLA-B27.

IF 5.7 2区 医学 Q1 RHEUMATOLOGY
Brian Wu, Amy Tang, Akihiro Nakamura
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引用次数: 0

Abstract

Purpose of review: Axial spondyloarthritis (axSpA) is a chronic multi-organ rheumatic disease affecting various tissues, and recent key advancements have provided significant insight into understanding its immunopathology.

Recent findings: Expanded CD8⁺ T cell subsets bearing unique T cell receptor (TCR) motifs (TRAV21/TRBV9) in HLA-B27-positive axSpA patients or those with acute anterior uveitis were recently identified. These T cells can bind to self- and bacterial-derived peptides, supporting the "arthritogenic peptide" hypothesis. Monoclonal antibody-mediated elimination of these expanded T cells has shown potential as a novel treatment for axSpA in a phase II clinical trial, offering a groundbreaking therapeutic approach. In addition to T cells, neutrophils have emerged as important mediators of both inflammation and new bone formation in axSpA, potentially contributing to HLA-B27-independent immune pathomechanisms. Key neutrophil-derived molecules-such as macrophage migration inhibitory factor, hypoxia-inducible factor 1-alpha, caspase recruitment domain-containing protein 9, and neutrophil extracellular traps (NETs)-have been shown in preclinical models to promote Th17-mediated inflammation and reduce regulatory T cell numbers. These mechanisms may be relevant to axSpA pathogenesis and represent potential new therapeutic targets. In recent years, significant progress has been made in understanding the immunopathology of axSpA through both HLA-B27-dependent and -independent mechanisms. However, key questions remain. The pathogenic HLA-B27:05-bound peptides driving CD8⁺ T cell expansion remain unidentified. Moreover, due to the diversity of TCR motifs that recognize self- and microbial peptides, therapies targeting a single TCR (e.g., TRBV9) may have limited efficacy. Further research is needed to clarify axSpA pathogenesis across both pathways.

轴型脊柱性关节炎的免疫病理研究进展:伴和不伴HLA-B27。
综述目的:轴性脊柱炎(axSpA)是一种影响多种组织的慢性多器官风湿病,最近的关键进展为理解其免疫病理学提供了重要的见解。最近发现:hla - b27阳性axSpA患者或急性前葡萄膜炎患者中扩增的CD8 + T细胞亚群携带独特的T细胞受体(TCR)基元(TRAV21/TRBV9)。这些T细胞可以结合自身和细菌衍生的肽,支持“关节炎肽”假说。在一项II期临床试验中,单克隆抗体介导的消除这些扩增的T细胞已显示出作为axSpA新治疗方法的潜力,提供了一种突破性的治疗方法。除T细胞外,中性粒细胞已成为axSpA中炎症和新骨形成的重要介质,可能参与不依赖hla - b27的免疫病理机制。关键的中性粒细胞衍生分子,如巨噬细胞迁移抑制因子、缺氧诱导因子1- α、caspase募集结构域蛋白9和中性粒细胞胞外陷阱(NETs),已在临床前模型中显示可促进th17介导的炎症并减少调节性T细胞数量。这些机制可能与axSpA的发病机制有关,并代表着潜在的新的治疗靶点。近年来,通过hla - b27依赖性和非依赖性机制对axSpA免疫病理的理解取得了重大进展。然而,关键问题依然存在。驱动CD8 + T细胞扩增的致病性hla - b27:05结合肽仍未确定。此外,由于识别自身和微生物肽的TCR基序的多样性,针对单一TCR(例如TRBV9)的治疗可能疗效有限。需要进一步的研究来阐明axSpA在这两种途径中的发病机制。
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来源期刊
CiteScore
11.20
自引率
0.00%
发文量
41
期刊介绍: This journal aims to review the most important, recently published research in the field of rheumatology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care and prevention of rheumatologic conditions. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas such as the many forms of arthritis, osteoporosis and metabolic bone disease, and systemic lupus erythematosus. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also occasionally provided.
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