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Crohn's & Colitis
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Mass cytometry distinguishes between Crohn’s disease and Ulcerative colitis

Identification of better markers using less invasive methods would enable earlier diagnosis as well as improved monitoring and treatment of both diseases.

CD and UC can be distinguished clinically by disease location (UC is restricted to the colon, while CD can involve any part of the gastrointestinal tract) and disease phenotype (stricturing or penetrating can indicate CD), using endoscopy and imaging5. However, gathering this information can be invasive and costly, and still up to 20% of IBD cases with colonic disease are indeterminate10. About 10% of patients who undergo colectomy for perceived UC are subsequently diagnosed with CD previously confined to the colon10,11.

Despite roles of host genetics, the immune system, the microbiota, and the environment in the pathogenesis of IBD4, factors responsible for the breadth of disease manifestations between patients (heterogeneity) are not well defined. Identifying and monitoring the symptoms, severity, behavior, and therapeutic response that characterize each disease manifestation (phenotype) is critical for improving health, yet frequently requires the use of invasive procedures, such as endoscopy.

In the tissue, IBD is characterized by intestinal barrier breakdown, allowing microbiota to prime the immune system. The ensuing inflammatory response involves recruitment of leukocytes from the periphery to the gut and is associated with dissemination of activated cells in circulation2,12,13. Since leukocytes that traffic to the gut from the periphery mediate this inflammatory response, we hypothesized that, by enriching for gut tropic cells in the blood, we could detect CD- and UC-specific as well as phenotype-specific signatures and investigate their relationship to the tissue. Since blood is easily accessible, identification of immune signatures in circulation that represent intestinal immunity would be highly informative and provide less invasive tools to assess disease.

Our findings are consistent with distinct responses in circulation and tissue as well as CD4+ T cells in CD51. We identified additional cells, many accessible in the blood, that reflected disease group distinctions. Although disease-specific leukocytes reside mostly in affected tissues51, using gut-trafficking molecules we enriched for disease-specific cells in blood and demonstrated their utility in defining disease groups. We uncovered signatures of disease diagnosis (CD vs. UC), state (flare vs. remission), and phenotypes (behavior and location).

Consistent with clinical observations, we found greater cellular heterogeneity among CD compared with UC. Blood signatures could be developed as non-invasive, cost-effective, and safe markers for disease diagnosis and monitoring. Although our classification model could be over specified and there exist cellular features not tested here, these limitations do not interfere with its potential utility. Future validation using larger independent cohort(s) will be necessary.

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Posted on: June 28 2019

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Crohns & Colitis