{"title":"Recent Advances in the Immunopathology of Axial Spondyloarthritis: with and without HLA-B27.","authors":"Brian Wu, Amy Tang, Akihiro Nakamura","doi":"10.1007/s11926-025-01194-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":"27 1","pages":"27"},"PeriodicalIF":5.7000,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Rheumatology Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11926-025-01194-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
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.
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.