小柯机器人

荷兰格罗宁根大学医学中心Rinse K. Weersma团队近期取得重要工作进展。他们研究通过炎症性肠病中抗体表位库的噬菌体展示免疫沉淀测序揭示了不同的抗体特征。相关研究成果2023年5月9日在线发表于《免疫》杂志上。

据介绍，炎症性肠病（IBD），如克罗恩病（CD）和溃疡性结肠炎（UC），是一种慢性免疫介导的炎症性疾病。然而，缺乏对IBD特异性抗体表位库的全面综述。

使用高通量噬菌体展示免疫沉淀测序（PhIP-Seq），研究人员在497名IBD患者和1326名对照患者中鉴定出344,000种抗微生物、免疫和食物抗原的抗体。IBD的特征是373种差异丰富的抗体反应（202种过度表达，171种不足表达），其中17%由两种IBD共享，55%为CD独有，28%为UC独有。针对细菌鞭毛蛋白的抗体反应性在CD中占主导地位，与回肠受累、纤维狭窄性疾病和抗酿酒酵母抗体阳性有关，但与粪便微生物组成无关。抗体表位库准确地将CD与对照区分开来（曲线下面积[AUC]=0.89），当仅使用10种抗体时也实现了类似的区分（AUC=0.87）。

因此，IBD患者对所选肽表现出独特的的抗体库，从而允许临床分层和发现免疫靶点。

附：英文原文

Title: Phage-display immunoprecipitation sequencing of the antibody epitope repertoire in inflammatory bowel disease reveals distinct antibody signatures

Author: Arno R. Bourgonje, Sergio Andreu-Sánchez, Thomas Vogl, Shixian Hu, Arnau Vich Vila, Ranko Gacesa, Sigal Leviatan, Alexander Kurilshikov, Shelley Klompus, Iris N. Kalka, Hendrik M. van Dullemen, Adina Weinberger, Marijn C. Visschedijk, Eleonora A.M. Festen, Klaas Nico Faber, Cisca Wijmenga, Gerard Dijkstra, Eran Segal, Jingyuan Fu, Alexandra Zhernakova, Rinse K. Weersma

Issue&Volume: 2023-05-09

Abstract: Inflammatory bowel diseases (IBDs), e.g., Crohn’s disease (CD) and ulcerative colitis(UC), are chronic immune-mediated inflammatory diseases. A comprehensive overviewof an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughputphage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodiesagainst 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBDcompared with 1,326 controls. IBD was characterized by 373 differentially abundantantibody responses (202 overrepresented and 171 underrepresented), with 17% sharedby both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities againstbacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenoticdisease, and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitoperepertoires accurately discriminated CD from controls (area under the curve [AUC] =0.89), and similar discrimination was achieved when using only ten antibodies (AUC =0.87). Individuals with IBD thus show a distinct antibody repertoire against selectedpeptides, allowing clinical stratification and discovery of immunological targets.

DOI: 10.1016/j.immuni.2023.04.017

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00185-1

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