Abstract Background Individuals with inflammatory bowel diseases (IBD) show multiple dysregulated immune responses toward the gut microbiome and mycobiome, as well as against several herpes viruses, mainly Epstein-Barr virus. Although the T cell repertoire has been extensively investigated, the B cell repertoire remains poorly understudied. Novel antibodies targeting yet-to-be-discovered antigens implicated in Crohn’s disease (CD) can be discovered by investigating the B cell repertoire. Methods We profiled the B cell repertoire of 24 treatment-naive individuals with CD and 24 age- and sex- matched symptomatic controls (SCs), from the Norwegian inception cohort IBSEN III1. Results Individuals with CD exhibited a reduced diversity in their B cell repertoire relative to symptomatic controls. This reduction was evidenced at the level of Shannon (Fig. 1A) and Simpson (Fig. 1B) diversity. The repertoire of individuals with CD also harbored markers of antigenic exposures and was dominated by highly expanded clones (Fig. 1C). This excessive antigenic expansion was also detected at the heavy chain (IGH) repertoire level, where we observed a less contribution of the IgM and IgD encoding IGH chains, and a more expansion of IgA2 and IgG2 responses (Fig. 1D). Conclusion Our results show that individuals with CD have an excessive antigenic exposure in their B cell repertoire, the expanded response is geared toward the generation of IgA2 secreted antibodies, and the proinflammatory IgG2 immune responses. Future efforts shall aim at identifying the antigens targeted by these expanded clones to be identify B cell responses and antigenic exposures implicated in the disease. Reference: 1. Kristensen, V. A. et al. Inflammatory bowel disease in South-Eastern Norway III (IBSEN III): a new population-based inception cohort study from South-Eastern Norway. Scand J Gastroenterol 56, 899–905 (2021). Conflict of interest: Dr. Mahdy, Aya: I do not have a conflict of interest. Taheri, Zahra: No conflict of interest Høivik, Marte: M.L.H. received investigator-initiated research grants from Takeda, Pfizer, Tilllotts, Ferring, and Janssen. Speaker honoraria from Takeda, Tillotts, Ferring, AbbVie, Galapagos, and Meda. She is also on the advisory board of Takeda, Galapagos, MSD, Lilly, and AbbVie. All other co-authors declare no competing interests. Franke, Andre: I have no conflicts of interest. ElAbd, Hesham: I do not have a conflict of interest.
Mahdy et al. (Thu,) studied this question.