Collagenous Colitis Is Associated With HLA Signature and Shares Genetic Risks With Other Immune-Mediated Diseases

Letter to the Editor: Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: A Meta-analysis of Individual Patient Data

“…Emerging evidence suggests that similar to classical IBD, the disease occurs as a result of an aberrant immune response to the luminal microenvironment in a genetically susceptible host. First, genetic association studies have shown that variants within HLA genes are associated with risk of MC, 2,[4][5][6] similar to other chronic diseases with aberrant immune response to the gut microenvironment (ie, celiac disease 33 and classical IBD 34 ). Second, human translational studies have demonstrated complete histologic remission with fecal diversion (ie, creation of an ileostomy bag) in patients with refractory disease, and recurrence of histologic inflammation after reestablishing the fecal stream, [35][36][37] underscoring the critical role of gut microbiota in the pathogenesis of MC.…”

“…Although it is unclear how microbiome changes can trigger an immune response, genetic association studies have suggested a possible link between genes coding for MHC molecules, [3][4][5][6] which are involved in recognition of extracellular pathogens by innate immunity, and risk of MC. This raises the possibility that gastrointestinal infections either directly or through alteration of the gut microenvironment may lead to T-cell activation through MHC molecules.…”

“…1 Genetic associations with the HLA region have been detected for MC in early small candidate studies, 2 and later larger Immunochip analyses, 3,4 which were consistently replicated in independent cohorts and biobanks. 5,6 Increased risk of CC, but not LC, 3,4 was observed in relation to an extended haplotype (8.1) that includes several genes coding for major histocompatibility complex (MHC) molecules with a critical role in immune response to microbial pathogens. This observation supports the hypothesis that enteric infection through its effect on innate immune system and the community structure and function of the gut microbiome may increase risk of MC.…”

Transcriptomic Profiling of Collagenous Colitis Identifies Hallmarks of Nondestructive Inflammatory Bowel Disease

“…A substantial number of pathways also contained genes of the response to interferons (IFNs) (Figure 1D and 2; Supplementary Table 1). Of note, human leukocyte antigen (HLA)-I and -II genes that were previously associated with CC 7,14 have an increased expression in active CC (Figures 1-2). Collectively, our results corroborate the genetic association with HLA, and indicate immune response activation and bacterial recognition in CC pathogenesis.…”

Editorial: the microscope holds the key to predict need for biologic therapy in immunotherapy‐checkpoint inhibitory colitis. Authors' reply

“…We completely agree that the association between the microscopic colitis pattern of injury, age and duration of ICI treatment deserves more exploration. The type of microscopic pattern observed may reflect different underlying genetic susceptibilities, some of which have been associated with IBD and microscopic colitis 6,7 . It is also unknown if these different histological patterns require tailored therapy for optimal patient management.…”