A B-Cell Gene Signature Correlates With the Extent of Gluten-Induced Intestinal Injury in Celiac DiseaseSummary

• Published in: Cellular and molecular gastroenterology and hepatology Vol. 4; no. 1; pp. 1 - 17
• Main Authors: Mitchell E. Garber, Alok Saldanha, Joel S. Parker, Wendell D. Jones, Katri Kaukinen, Kaija Laurila, Marja-Leena Lähdeaho, Purvesh Khatri, Chaitan Khosla, Daniel C. Adelman, Markku Mäki
• Format: Journal Article
• Language: English
• Published: Elsevier 01.07.2017
• ISSN: 2352-345X

Background & Aims: Celiac disease (CeD) provides an opportunity to study autoimmunity and the transition in immune cells as dietary gluten induces small intestinal lesions. Methods: Seventy-three celiac disease patients on a long-term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A peripheral blood sample and intestinal biopsy specimens were taken before and 6 weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus-heightâtoâcrypt-depth ratio to quantify gluten-induced intestinal injury. Pooled B and T cells were isolated from whole blood, and RNA was analyzed by DNA microarray looking for changes in peripheral B- and T-cell gene expression that correlated with changes in villus height to crypt depth, as patients maintained a relatively healthy intestinal mucosa or deteriorated in the face of a gluten challenge. Results: Gluten-dependent intestinal damage from baseline to 6 weeks varied widely across all patients, ranging from no change to extensive damage. Genes differentially expressed in B cells correlated strongly with the extent of intestinal damage. A relative increase in B-cell gene expression correlated with a lack of sensitivity to gluten whereas their relative decrease correlated with gluten-induced mucosal injury. A core B-cell gene module, representing a subset of B-cell genes analyzed, accounted for the correlation with intestinal injury. Conclusions: Genes comprising the core B-cell module showed a net increase in expression from baseline to 6 weeks in patients with little to no intestinal damage, suggesting that these individuals may have mounted a B-cell immune response to maintain mucosal homeostasis and circumvent inflammation. DNA microarray data were deposited at the GEO repository (accession number: GSE87629; available: https://www.ncbi.nlm.nih.gov/geo/). Keywords: Oral Tolerance, Mucosal Immunity, Autoimmunity, Regulatory B Cell