bioRxiv : the preprint server for biology · 2026
Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease.
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Gubatan John, Ye Jiayu, Lund-Andersen Christin, Canas Jorge, Zhou Yuxi, Boye Theresa, Hoang Jacqueline, Sojwal Raoul S, Fardeen Touran, Tran Tracy, Sokzini Peacha, Koh Ally Hamin, Gibson Marielle, Huang Yuting, Peterson Kathryn, Sinha Sidhartha R, Rogalla Stephan, Nielsen Ole Haagen, Rosen Michael J, Sandve Geir Kjetil
Аннотация
UNLABELLED: 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.
HIGHLIGHTS: Paired single-cell receptors map circulating adaptive immune states across IBDTCR expansion and paired-chain convergence identify inflammatory programsBCR lineage maturation links plasma programs to mutation and class switchingRepertoire features benchmark diagnosis and clinical-state classification.
IN BRIEF: Gubatan et al. present a peripheral blood single-cell transcriptome and paired immune-receptor atlas across IBD and controls. Clone-aware analyses connect TCR expansion and sequence similarity to inflammatory programs, distinguish B-cell phenotype from lineage maturation, and link participant-level T-B covariation to an inferred ligand- receptor interactome. Machine learning models with repertoire features classify diagnosis, inflammatory status, and contemporaneous six-month treatment-response status.
HIGHLIGHTS: Paired single-cell receptors map circulating adaptive immune states across IBDTCR expansion and paired-chain convergence identify inflammatory programsBCR lineage maturation links plasma programs to mutation and class switchingRepertoire features benchmark diagnosis and clinical-state classification.
IN BRIEF: Gubatan et al. present a peripheral blood single-cell transcriptome and paired immune-receptor atlas across IBD and controls. Clone-aware analyses connect TCR expansion and sequence similarity to inflammatory programs, distinguish B-cell phenotype from lineage maturation, and link participant-level T-B covariation to an inferred ligand- receptor interactome. Machine learning models with repertoire features classify diagnosis, inflammatory status, and contemporaneous six-month treatment-response status.