Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Immunity. 2023 Jun 13;56(6):1393-1409.e6. doi: 10.1016/j.immuni.2023.04.017. Epub 2023 May 9.
Inflammatory bowel diseases (IBDs), e.g., Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. Using high-throughput phage-display immunoprecipitation sequencing (PhIP-Seq), we identified antibodies against 344,000 antimicrobial, immune, and food antigens in 497 individuals with IBD compared with 1,326 controls. IBD was characterized by 373 differentially abundant antibody responses (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD, and 28% unique to UC. Antibody reactivities against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease, and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires 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 selected peptides, allowing clinical stratification and discovery of immunological targets.
炎症性肠病（IBD），例如克罗恩病（CD）和溃疡性结肠炎（UC），是慢性免疫介导的炎症性疾病。然而，对于 IBD 特异性抗体表位谱缺乏全面的了解。使用高通量噬菌体展示免疫沉淀测序（PhIP-Seq），我们在 497 名 IBD 患者和 1326 名对照中分别鉴定出针对 344000 种抗菌、免疫和食物抗原的抗体。与对照组相比，IBD 具有 373 种差异丰富的抗体反应（202 种过度表达和 171 种低表达），其中 17%在两种 IBD 中共享，55%在 CD 中独特，28%在 UC 中独特。CD 中以细菌鞭毛蛋白的抗体反应为主，与回肠受累、纤维狭窄性疾病和抗酿酒酵母抗体阳性有关，但与粪便微生物组组成无关。抗体表位谱可准确区分 CD 与对照组（曲线下面积[AUC]为 0.89），仅使用 10 种抗体也可达到类似的区分效果（AUC 为 0.87）。因此，IBD 患者表现出针对选定肽的独特抗体谱，从而能够进行临床分层和免疫靶标的发现。
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