Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group

• Published in: Inflammatory bowel diseases Vol. 19; no. 13; pp. 2820 - 2828
• Main Authors: Pigneur, Bénédicte, Escher, Johanna, Elawad, Mamoun, Lima, Rosa, Buderus, Stephan, Kierkus, Jaroslaw, Guariso, Graziella, Canioni, Danielle, Lambot, Karen, Talbotec, Cécile, Shah, Neil, Begue, Bernadette, Rieux-Laucat, Frédéric, Goulet, Olivier, Cerf-Bensussan, Nadine, Neven, Bénédicte, Ruemmele, Frank M
• Format: Journal Article
• Language: English
• Published: England 01.12.2013
• Subjects: Adolescent; Age of Onset; Child; Child, Preschool; Colitis, Ulcerative - genetics; Crohn Disease - genetics; Female; Follow-Up Studies; Humans; Infant; Interleukin-10 - genetics; Interleukin-10 Receptor beta Subunit - genetics; Male; Mutation - genetics; Phenotype; Prognosis; Receptors, Interleukin - genetics
• ISSN: 1078-0998; 1536-4844
• DOI: 10.1097/01.MIB.0000435439.22484.d3

Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution. Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells. A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohn's disease-like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohn's disease-like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti-tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious. The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon.