Somatic mutations in coeliac disease and other enteropathies: From chronic inflammation to clonal immune disease

Somatic mutations are increasingly implicated in persistent intestinal inflammation in chronic enteropathies. This review examines how mutation-bearing immune and epithelial clones may emerge, expand and contribute to disease within the chronically inflamed gut. We focus on refractory coeliac disease, highlighting the recent evidence for lymphoma-associated mutations in expanded intraepithelial lymphocyte clones in both type I and type II disease. We then consider emerging evidence in other enteropathy, including autoimmune enteropathy, common carriable immunodeficiency-associated enteropathy and inflammatory bowel disease. Finally, we discuss how inflammation shapes clonal selection in the intestine, approaches for detecting low-frequency somatic variants, and the potential implications of mutation profiling for diagnosis, risk stratification and future therapeutic strategies.