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B细胞受体的综合分析揭示了免疫球蛋白a肾病中明显的λ轻链景观

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-07-12 DOI:10.1016/j.intimp.2025.115187

Wei-Tzu Luo , Chih-Chin Kao , Che-Mai Chang , Mei-Yi Wu , Hsin-Ni Liao , Szu-Ying Ho , I-Lin Tsai , Sheng-Po Chou , Mai-Szu Wu , Wei-Chiao Chang

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引用次数: 0

摘要

免疫球蛋白A肾病（IgAN）或伯杰氏病是一种自身免疫性肾脏疾病。它是由免疫球蛋白A （IgA）在肾脏中的沉积引起的，导致肾小球肾炎和肾功能的逐渐丧失。抗体/B细胞受体（BCR）如何参与IgAN的发病机制尚不清楚，因此，研究IgAN中的BCR库对于了解IgAN的病理生理机制至关重要。方法本研究通过免疫受体测序，对IgAN和非IgAN肾病（non-IgAN）患者的BCR全库，包括BCR重链（IGA、IGD、IGE、IGG和IGM）和轻链（IGL和IGK）进行全面分析。结果与非IgAN患者相比，IgAN患者BCR轻链库的多样性明显更高。此外，在IgAN患者中观察到更高的lambda轻链使用。进一步的网络分析表明，IgAN患者的BCR lambda轻链库更多样化，并鉴定出IgAN相关的lambda轻链克隆谱系，其使用的IGLV基因存在差异。结论BCR轻链库在IgAN患者中具有明显的不同特征，提示BCR轻链库的特征很有可能作为IgAN诊断的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Comprehensive analysis of B cell receptor repertoires reveals a distinct lambda light chain landscape in immunoglobulin A nephropathy

Background

Immunoglobulin A nephropathy (IgAN) or Berger's disease is an autoimmune kidney disease. It is caused by the deposition of immunoglobulin A (IgA) in the kidney that results in glomerulonephritis and a gradual loss of renal functions. How antibodies/B cell receptors (BCRs) are involved in the pathogenesis of IgAN remains unclear, thus, to investigate BCR repertoire in IgAN is crucial to understand pathophysiological mechanisms of IgAN.

Methods

In this study, whole BCR repertoire, including BCR heavy (IGA, IGD, IGE, IGG, and IGM) and light (IGL and IGK) chains, were comprehensively profiled and analyzed in IgAN and non-IgA nephropathy (non-IgAN) patients through immune receptor sequencing.

Results

We identified a significantly higher diversity in the BCR light chain repertoire in IgAN patients compared to non-IgAN patients. Additionally, a higher usage of lambda light chains was observed in IgAN patients. Further network analysis indicated a greater diversification of the BCR lambda light chain repertoire in IgAN patients and identified IgAN-associated lambda light chain clonal lineages with the differentially utilized IGLV gene.

Conclusion

These findings indicated significantly distinct features of BCR light chain repertoire in IgAN patients and suggested that characteristics of BCR light chain repertoire are very likely as potential biomarkers for the diagnosis of IgAN.

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来源期刊

International immunopharmacology

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.

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