Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease

Gubatan, J.; Ye, J.; Lund-Andersen, C.; Canas, J.; Zhou, Y.; Boye, T.; Hoang, J.; Sojwal, R.; Fardeen, T.; Tran, T.; Sokzini, P.; Koh, A. H.; Gibson, M.; Huang, Y.; Peterson, K.; Sinha, S.; Rogalla, S.; Nielsen, O. H.; Rosen, M. J.; Sandve, G. K.

doi:10.64898/2026.09.20.753043

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bioRxiv · 10.64898/2026.09.20.753043

Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease

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Abstract

Single-cell studies have defined immune states in inflammatory bowel disease (IBD), but how adaptive receptor histories organize circulating immunity remains unclear. We generated a single-cell transcriptomic atlas of peripheral blood from 249 participants with Crohn's disease, ulcerative colitis, or non-IBD control status, including 182 with productive TCR and BCR recovery. Expanded TCR clonotypes marked inflammatory-memory and cytotoxic states, while distinct but similar paired TCRs shared inflammatory programs across participants. BCR lineage maturation linked IgA-associated mucosal and plasma B cell programs to somatic mutation and class switching, distinguishing maturation-associated biology from clonal expansion. Helper, regulatory, and cytotoxic T-cell programs covaried with B-cell states, and inferred interactions nominated reciprocal antigen-presentation and helper pathways. Repertoire-based machine learning distinguished diagnosis, inflammation, and contemporaneous six-month treatment-response status. Together, this atlas connects receptor architecture to coordinated systemic immune remodeling, establishes a foundation for repertoire-informed patient stratification, and prioritizes candidate mechanisms of IBD pathogenesis.

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Gubatan, J., Ye, J., Lund-Andersen, C., Canas, J., Zhou, Y., Boye, T., Hoang, J., Sojwal, R., Fardeen, T., Tran, T., Sokzini, P., Koh, A. H., Gibson, M., Huang, Y., Peterson, K., Sinha, S., Rogalla, S., Nielsen, O. H., Rosen, M. J., Sandve, G. K.. 2026-09-23. Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease. https://doi.org/10.64898/2026.09.20.753043

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