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Inflamm Bowel Dis. 2013 Dec;19(13):2820-8. doi: 10.1097/01.MIB.0000435439.22484.d3.

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.

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1
*Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France; †Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France; ‡Department of Pediatric Gastroenterology, ErasmusMC-Sophia Children's Hospital, Rotterdam, the Netherlands; §Department of Gastroenterology, Great Ormond Street Hospital for Sick Children and Institute of Child Health, London, United Kingdom; ‖Pediatric Gastroenterology Unit, Centro Hospitalar do Porto, Porto, Portugal; ¶Marienhospital, Bonn, Germany; **Department of Gastroenterology, Hepatology and Feeding Disorders, The Children's Memorial Health Institute, Warsaw, Poland; ††Gastroenterologia, Endoscopia Digestiva, Epatologia e Cura del Bambino con Trapianto di Fegato, Dipartimento Salute della Donna e del Bambino, Padova, Italy; ‡‡Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service d'anatomopathologie, Paris, France; §§Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de radiologie, Paris, France; ‖‖INSERM U989, Paris, France; and ¶¶INSERM U768, Paris, France.

Abstract

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'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.

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.

[Indexed for MEDLINE]

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