Category: Autoimmune rheumatologic diseases
Clinical overlap between Spondyloarthritis (SpA) and Crohn’s disease (CD) indicates they may share common pathogenic mechanisms originating in the intestinal mucosa. There is minimal data comparing these disease populations to each other and to patients having an overlap of the two conditions (CD-SpA). To uncover underlying immunologic commonalities between the disease states in an unbiased manner, we performed single cell RNA sequencing on viable CD45+ cells isolated from colon biopsies taken from 2 patients each with SpA, CD, and CD-SpA as well as 2 controls. In the SpA and IBD-SpA patients, we observed an expansion of a TCR-negative population that clustered with T-cells by TSNE. We hypothesized that these cells were ILCs. To validate this initial finding, we expanded our subject cohort to 62 individuals and assayed colon biopsy tissue for ILC expansion by flow cytometry. We observed increased ILC3s in the SpA and CD groups, and increased ILC1s in the CD-SpA group, in contrast to previously reported ILC1 expansion in Crohn’s. Additionally, while others have shown that the expanded ILC3 population in AS is primarily Natural-Cytotoxicity-Receptor positive (NCR+), we see the most significant increase in the NCR- population. Finally, the unique expansion of ILC1s in IBD-SpA implies the presence of a distinct disease process in affected individuals. In addition to confirming a role of ILC3 in the pathogenesis of SpA, these data suggest a role of ILC3s in CD and ILC1s in CD-SpA. Additional investigation will be needed to further elucidate the contribution of these populations to disease.
Adam Lefferts– Graduate Student, University of Colorado, Denver
Emilie Regner– University of Colorado, Denver
Rebecca O'Rourke– University of Colorado, Denver
Andrew Stahly– University of Colorado, Denver
Kenneth Jones– University of Colorado School of Medicine
Kristine Kuhn– University of Colorado, Denver