Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease
- 1Mayo Clinic
Abstract
SUMMARY 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. GRAPHICAL ABSTRACT Highlights Paired single-cell receptors map circulating adaptive immune states across IBD TCR expansion and paired-chain convergence identify inflammatory programs BCR lineage maturation links plasma programs to mutation and class switching Repertoire 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.
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BibTeX
@misc{gubatan2026singlecell,
title = {{Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease}},
author = {J. Gubatan and J. Ye and C. Lund-Andersen and J. Canas and Y. Zhou and T. Boye and J. Hoang and R. Sojwal and T. Fardeen and T. Tran and P. Sokzini and A. H. Koh and M. Gibson and Y. Huang and K. Peterson and S. Sinha and S. Rogalla and O. H. Nielsen and M. J. Rosen and G. K. Sandve},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.753043},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.753043v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Single-cell immune repertoire atlas maps coordinated circulating adaptive immune states in inflammatory bowel disease
AU - J. Gubatan
AU - J. Ye
AU - C. Lund-Andersen
AU - J. Canas
AU - Y. Zhou
AU - T. Boye
AU - J. Hoang
AU - R. Sojwal
AU - T. Fardeen
AU - T. Tran
AU - P. Sokzini
AU - A. H. Koh
AU - M. Gibson
AU - Y. Huang
AU - K. Peterson
AU - S. Sinha
AU - S. Rogalla
AU - O. H. Nielsen
AU - M. J. Rosen
AU - G. K. Sandve
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.753043
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.753043v1
AB - SUMMARY 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. GRAPHICAL ABSTRACT Highlights Paired single-cell receptors map circulating adaptive immune states across IBD TCR expansion and paired-chain convergence identify inflammatory programs BCR lineage maturation links plasma programs to mutation and class switching Repertoire 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.
ER -