Pesesky Mitchell, Bharanikumar Ramit, Le Bourhis Lionel, ElAbd Hesham, Rosati Elisa, Carty Cara L, Singh Namita, Bokemeyer Bernd, Schreiber Stefan, Görg Siegfried, Noceda Marco Garcia, Chapfuwa Paidamoyo, Gittelman Rachel M, May Damon, Dines Jennifer N, Zhou Wenyu, Kaplan Ian M, Snyder Thomas M, Jabran Zahid Harus, Greissl Julia, Chen-Harris Haiyin, Howie Bryan, Franke Andre, Robins Harlan S, Allez Matthieu
Adaptive Biotechnologies, Seattle, WA, United States.
Institut de Recherche Saint-Louis, Université Paris Cité, INSERM U1160, Paris, France.
J Crohns Colitis. 2025 Jul 3;19(7). doi: 10.1093/ecco-jcc/jjaf048.
Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are known to involve shifts in the T-cell repertoires of affected individuals, including clonal expansion of abundant T-cell populations in CD mucosal tissue. There are also differential human leukocyte antigen (HLA) risk and protective alleles between CD and UC, implying CD- and UC-specific repertoire changes that have not yet been identified. In this study, we aimed to identify specific, antigen-driven T-cell signatures in CD and UC.
We performed ImmunoSequencing on blood samples from 3853 CD cases, 1803 UC cases, and 5596 healthy controls (HCs). We identified public T cell receptor β (TCRB) sequences significantly enriched in CD or UC cases.
We determine that there is more expansion across clonotypes in CD, but not UC, compared with HCs. Strikingly, from blood, we identify public TCRBs specifically expanded in CD or UC. These sequences are more abundant in intestinal mucosal samples, form groups of similar CDR3 sequences, and can be associated with specific HLA alleles. Although the prevalence of these sequences is higher in ileal and ileocolonic CD than colonic CD or UC, the TCRB sequences themselves are shared across CD and not between CD and UC.
There are peptide antigens that commonly evoke immune reactions in IBD cases and rarely in non-IBD controls. These antigens differ between CD and UC. CD, particularly ileal CD, also seems to involve more substantial changes in clonal population structure than UC, compared to HCs.
炎症性肠病（IBD），包括克罗恩病（CD）和溃疡性结肠炎（UC），已知会导致患病个体的T细胞库发生变化，包括CD黏膜组织中丰富T细胞群体的克隆性扩增。CD和UC之间还存在不同的人类白细胞抗原（HLA）风险和保护性等位基因，这意味着尚未确定的CD和UC特异性库变化。在本研究中，我们旨在识别CD和UC中特定的、抗原驱动的T细胞特征。
我们对3853例CD患者、1803例UC患者和5596例健康对照（HC）的血样进行了免疫测序。我们确定了在CD或UC患者中显著富集的公共T细胞受体β（TCRB）序列。
我们确定，与HC相比，CD中克隆型的扩增更多，而UC中则不然。引人注目的是，我们从血液中识别出在CD或UC中特异性扩增的公共TCRB。这些序列在肠道黏膜样本中更为丰富，形成了相似CDR3序列的组，并且可以与特定的HLA等位基因相关联。尽管这些序列在回肠和回结肠CD中的患病率高于结肠CD或UC，但TCRB序列本身在CD之间是共享的，而不是在CD和UC之间共享。
在IBD病例中通常会引发免疫反应的肽抗原，在非IBD对照中很少引发。这些抗原在CD和UC之间有所不同。与HC相比，CD，尤其是回肠CD，似乎在克隆群体结构方面也比UC涉及更实质性的变化。
