• Daniel Kotlarz, Rita Beier, Dhaarini Murugan, Jana Diestelhorst, Ole Jensen, Kaan Boztug, Dietmar Pfeifer, Hans Kreipe, Eva-Doreen Pfister, Ulrich Baumann, Jacek Puchalka, Jens Bohne, Odul Egritas, Buket Dalgic, Kaija-Leena Kolho, Axel Sauerbrey, Stephan Buderus, Tayfun Güngör, Axel Enninger, Yu Kar Ling Koda, Graziella Guariso, Batia Weiss, Selim Corbacioglu, Piotr Socha, Nuray Uslu, Ayse Metin, Ghassan T Wahbeh, Khalid Husain, Dina Ramadan, Waleed Al-Herz, Bodo Grimbacher, Martin Sauer, Karl-Walter Sykora, Sibylle Koletzko, and Christoph Klein.
• Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
• Gastroenterology. 2012 Aug 1; 143 (2): 347-55.

Background & AimsHomozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder.MethodsWe analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT.ResultsUsing a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant.ConclusionsWe identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

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