孤舟蓑笠翁
(2025-06-13 20:26):
#paper 【doi】10.1038/s41591-025-03692-w；【发表年份】2025年；【期刊】Nature Medicine；【标题】T and B cell responses against Epstein-Barr virus in primary sclerosing cholangitis。该研究简略地探讨了EB病毒（EBV）与原发性硬化性胆管炎（PSC）的免疫关联，发现PSC患者的T/B细胞对EBV反应异常增强。具体通过比较504名PSC患者和904名健康人的T细胞受体（TCR）测序，鉴定出1008个PSC相关克隆型，其中多数靶向EBV抗原（如BZLF1和EBNA3），且受PSC风险HLA等位基因（如HLA-B*08:01）限制；通过噬菌体免疫沉淀测序（PhIP-seq）分析120名PSC和202名健康人血清，显示PSC患者抗EBV抗体反应显著升高（尤其靶向BMRF1等裂解期蛋白）；从PSC肝脏浸润B细胞提取的单克隆抗体也证实靶向EBV抗原（如BFRF3）；最后通过超116万人电子病历分析，发现传染性单核细胞增多症（EBV引起）患者患PSC风险比健康人高12倍（95% CI: 6.3-22.9），远高于其他免疫疾病（如克罗恩病），表明EBV感染与PSC发病存在强流行病学关联，提示EBV再激活可能在PSC病理中起关键作用。
Nature Medicine,
2025-6-11.
DOI: 10.1038/s41591-025-03692-w
T and B cell responses against Epstein–Barr virus in primary sclerosing cholangitis
Abstract:
Abstract<br> Primary sclerosing cholangitis (PSC) is an idiopathic, progressive and incurable liver disease. Here, we aimed for systematic analyses of adaptive immune responses in PSC. By profiling the T cell repertoires of 504 individuals with PSC and 904 healthy controls, we identified 1,008 clonotypes associated with PSC. A substantial fraction of these clonotypes was restricted to known PSC human leukocyte antigen susceptibility alleles and known to target Epstein–Barr virus (EBV) epitopes. We further utilized phage-immunoprecipitation sequencing to determine antibody epitope repertoires of 120 individuals with PSC and 202 healthy controls, which showed a higher burden of anti-EBV responses in PSC than controls. EBV-specific monoclonal antibodies isolated from B cells in PSC livers corroborated convergent B and T cell responses against EBV. By analyzing electronic health records of >116 million people, we identified an association between infectious mononucleosis and PSC (odds ratio, 12; 95% confidence interval, 6.3–22.9), suggesting a link between EBV and PSC.
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