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引用次数: 0
摘要
类风湿性关节炎是一种常见的自身免疫性疾病,但人们对其外周血中 B 细胞的特征却知之甚少。本研究通过高通量测序和生物信息学分析,对早期类风湿性关节炎(ERA)患者的外周血 IgM 重排进行了分析。结果发现,ERA 患者的 IgM 基因库中出现了克隆扩增。有趣的是,ERA 基因库中的部分优势克隆对多种自身抗原表现出自反应和多反应性。这些克隆也存在于健康成人的 IgM 反应库中,但它们并没有扩增,这表明它们可能来自天然的自身反应性 B 细胞反应库。此外,ERA 重排表现出更大程度的体细胞高突变,尤其是在ERA 优势克隆中,导致对抗原-抗体相互作用很重要的氨基酸富集。对 B 细胞复合物的深入分析增进了我们对早期类风湿性关节炎 IgM 复合物的了解,为了解该疾病的发病机制提供了潜在的线索。
Characteristics of the IgM Repertoires in the Peripheral Blood of Early Rheumatoid Arthritis Patients.
Rheumatoid arthritis is a common autoimmune disease, but little is known about the characteristics of the B cell repertoires in the peripheral blood. In this study, the peripheral IgM repertoires of early rheumatoid arthritis (ERA) patients were analyzed by high-throughput sequencing and bioinformatics analyses. Clonal expansion was observed in IgM repertoires of ERA patients. Interestingly, a subset of the dominant clones in ERA repertoires showed self- and poly-reactivity to several autoantigens. The clones were also present in IgM repertoires of healthy adults but they were not expanded, suggesting that may stem from the natural auto-reactive B cell repertoire. Additionally, the ERA repertoires exhibited a greater extent of somatic hypermutations, particularly in the ERA dominant clones, resulting in an enrichment of amino acids important for antigen-antibody interaction. The in-depth analysis of B-cell repertoires improved our knowledge of the IgM repertoires in early rheumatoid arthritis, offering potential insights into the disease's pathogenesis.
期刊介绍:
JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.