Simultaneous Profiling of the Blood and Gut T and B Cell Repertoires in Crohn's Disease and Symptomatic Controls Illustrates Tissue-specific Alterations in the Immune Repertoire of Crohn's Disease Patients

Aya K.H. Mahdy^1,2Valentina Schöpfel^1,2Gert Huppertz-Hauss³Gøri Perminow⁴Florian Tran^1,2Corinna Bang^1,2Johannes R Hov⁴May-Bente Bengtson⁵Petr Ricanek⁶Randi Opheim⁴Tone Bergene Aabrekk⁵Trond Espen Detlie⁷Vendel A Kristensen⁷Mathilde Poyet²Marte Lie Høivik^4,7Andre Franke²Hesham ElAbd^1,2*

• ¹Universitatsklinikum Schleswig-Holstein Campus Kiel, Kiel, Germany
• ²University of Kiel, Kiel, Germany
• ³Sykehuset Telemark HF, Skien, Norway
• ⁴Oslo universitetssykehus Rikshospitalet, Oslo, Norway
• ⁵Sykehuset i Vestfold HF, Tønsberg, Norway
• ⁶Lovisenberg Diakonale Sykehus AS, Oslo, Norway
• ⁷Universitetet i Oslo, Oslo, Norway

Crohn's disease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome.We have shown that the T cell repertoire of CD patients harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. To profile the immunological signature of CD at a high-resolution we simultaneously profiled the αβ and γδ T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa for 27 treatmentnaïve CD patients and 27 age-matched symptomatic controls. Regardless of disease, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of CD patients relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa.These include a depletion of mucosal-associated invariant T (MAIT) cells in the blood repertoire, an expansion of TRAV29/DV5-TRAJ5 + clonotypes and a significant depletion of multiple IGHV3-33-IGHJ4 + and IGHV3-33-IGHJ6 + clonotypes in the blood and gut IGH repertoire of CD patients. In conclusion, our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues.