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

作者：Pigneur Benedicte; Escher Johanna; Elawad Mamoun; Lima Rosa; Buderus Stephan; Kierkus Jaroslaw; Guariso Graziella; Canioni Danielle; Lambot Karen; Talbotec Cecile; Shah Neil; Begue Bernadette; Rieux Laucat Frederic; Goulet Olivier; Cerf Bensussan Nadine; Neven Benedicte; Ruemmele Frank M^*

来源：Inflammatory Bowel Diseases, 2013, 19(13): 2820-2828.

DOI：10.1097/01.MIB.0000435439.22484.d3

• early-onset inflammatory bowel disease
• IL10 deficiency
• pediatric

Objective: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.Design: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.Results: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%26apos;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%26apos;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.Conclusion: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.

• 出版日期2013-12