Rubin SJS^1,2, Bai L^1,2, Haileselassie Y², Garay G³, Yun C^2,4, Becker L², Streett SE², Sinha SR², Habtezion A^5,6. Nat Commun. 2019 Jun 19;10(1):2686. doi: 10.1038/s41467-019-10387-7.

Author information

1 Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA, 94305, USA.

2 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Alway Building M211, 300 Pasteur Drive, Stanford, CA, 94305, USA.

3 Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Alway Building M211, 300 Pasteur Drive, Stanford, CA, 94305, USA.

4 Clinical Research - Inflammation and Respiratory Therapeutic Area, Gilead Sciences, 333 Lakeside Drive, Foster City, CA, 94404, USA.

5 Immunology Program, Stanford University School of Medicine, 1215 Welch Road, Modular B, Stanford, CA, 94305, USA. aidah@stanford.edu.

6 Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Alway Building M211, 300 Pasteur Drive, Stanford, CA, 94305, USA. aidah@stanford.edu.

Abstract

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. Each disease is characterized by a diverse set of potential manifestations, which determine patients' disease phenotype. Current understanding of phenotype determinants is limited, despite increasing prevalence and healthcare costs. Diagnosis and monitoring of disease requires invasive procedures, such as endoscopy and tissue biopsy. Here we report signatures of heterogeneity between disease diagnoses and phenotypes. Using mass cytometry, we analyze leukocyte subsets, characterize their function(s), and examine gut-homing molecule expression in blood and intestinal tissue from healthy and/or IBD subjects. Some signatures persist in IBD despite remission, and many signatures are highly represented by leukocytes that express gut trafficking molecules. Moreover, distinct systemic and local immune signatures suggest patterns of cell localization in disease. Our findings highlight the importance of gut tropic leukocytes in circulation and reveal that blood-based immune signatures differentiate clinically relevant subsets of IBD.