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Deep analysis of the peripheral immune system in IBD reveals new insight in disease subtyping and response to monotherapy or combination therapy

Kosoy et al. CMGH (2021)
Despite their opposing effects on a broad range of B cell subsets, the combination of thiopurine and anti-TNF treatments results in targeted effects on a single B cell subset offering new therapeutic potential.
Despite their opposing effects on a broad range of B cell subsets, the combination of thiopurine and anti-TNF treatments results in targeted effects on a single B cell subset offering new therapeutic potential.

Can we use blood tests to track the immune status of a localized disorder, such as inflammatory bowel disease (IBD)? Using mass cytometry’s high-resolution capability, Kosoy et al. from the Icahn School of Medicine answer “yes.” 

In this large immune profiling cohort of IBD patients, the researchers tested blood from 728 Crohn’s disease, 464 ulcerative colitis, and 334 control patients using 10 flow cytometry and 38 mass cytometry surface markers. Several key immune cell signatures were uncovered concerning disease diagnosis, state, phenotypes, and medication use. Compared to ulcerative colitis, patients with Crohn’s disease have more Th1Th17 and memory CD4 T cells, but fewer total T cells, Th1 cells, and CD4+CD8+ T cells, verifying previously observed differences in Th1/Th17 balance between IBD subsets.

The scientists also found immature CD27B cells were reduced in both Crohn’s disease and ulcerative colitis. Interestingly, while anti-tumor necrosis factor antibodies increase the total B cell pool and thiopurine decreases it, patients on combination therapy showed a significant reduction in only the immature CD27 B cells with improved clinical benefit. 

This finding highlights mass cytometry’s ability to identify immune cell subsets reshaped by therapies. It also exhibits how immune profiling can help narrow down the key targets when broad-acting therapies are used in combination.

Reference Citation

  1. Kosoy R, Kim-Schulze S, Rahman A, Friedman JR, Huang R, Peters LA, Amir E, Perrigoue J, Stojmirovic A, Song W, Ke H, Ungaro R, Mehandru S, Cho J, Dubinsky M, Curran M, Brodmerkel C, Schadt EE, Sands BE, Colombel J, Kasarskis A, Argmann CA, Suárez-Fariñas M (2021). Deep analysis of the peripheral immune system in IBD reveals new insight in disease subtyping and response to monotherapy or combination therapy. Cellular and Molecular Gastroenterology and Hepatology 12(2):599-632. doi: 10.1016/j.jcmgh.2021.03.012

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