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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Loss of interleukin-10 signaling and infantile inflammatory bowel disease: Implications for diagnosis and therapy
Gastroenterology, Volume 143, No. 2, Year 2012
Notification
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Description
Background & Aims: Homozygous 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. Methods: We 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. Results: Using 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. Conclusions: We 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. © 2012 AGA Institute.
Authors & Co-Authors
Kotlarz, Daniel
Germany, Hannover
Hannover Medical School
Germany, Munich
Klinikum Der Universität München
Beier, Rita
Germany, Hannover
Hannover Medical School
Murugan, Dhaarini
Germany, Hannover
Hannover Medical School
Germany, Munich
Klinikum Der Universität München
Diestelhorst, Jana
Germany, Hannover
Hannover Medical School
Germany, Munich
Klinikum Der Universität München
Jensen, Ole
Germany, Hannover
Hannover Medical School
Germany, Munich
Klinikum Der Universität München
Boztug, Kaan
Germany, Hannover
Hannover Medical School
Pfeifer, Dietmar
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Kreipe, Hans
Germany, Hannover
Hannover Medical School
Pfister, Eva Doreen
Germany, Hannover
Hannover Medical School
Baumann, Ulrich H.
Germany, Hannover
Hannover Medical School
Puchałka, Jacek
Germany, Munich
Klinikum Der Universität München
Bohne, Jens
Germany, Hannover
Hannover Medical School
Egritas, Odul
Turkey, Ankara
Gazi Üniversitesi
Dalgic, Buket
Turkey, Ankara
Gazi Üniversitesi
Kolho, Kaíja Leena
Finland, Helsinki
Children's Hospital Helsinki
Sauerbrey, Axel
Germany, Erfurt
Helios Klinikum Erfurt
Buderus, Stephan
Germany, Bonn
St. Marien Hospital, Bonn
Güngör, Tayfun
Switzerland, Zurich
Kinderspital Zürich
Enninger, Axel
Germany, Stuttgart
Klinikum Stuttgart Olgahospital
Koda, Yu Kar Ling
Brazil, Sao Paulo
Universidade de São Paulo
Guariso, Graziella
Italy, Padua
Università Degli Studi Di Padova
Weiss, Batia
Israel, Tel Aviv-yafo
Edmond and Lily Safra Children's Hospital
Corbacioglu, Selim
Germany, Regensburg
Klinikum Der Universität Regensburg Und Medizinische Fakultät
Socha, Piotr
Poland, Warsaw
Instytut Pomnik - Centrum Zdrowia Dziecka
Uslu, Nuray
Turkey, Ankara
Ankara Children's Hematology Oncology Training and Research Hospital
Metin, Ayşe
Turkey, Ankara
Ankara Children's Hematology Oncology Training and Research Hospital
Wahbeh, Ghassan T.
United States, Seattle
Seattle Children's Hospital
Husain, Khaled
Kuwait, Safat
Al-amiri Hospital
Ramadan, D. G.
Kuwait
Al-sabah Hospital
Al-Herz, Waleed
Kuwait
Al-sabah Hospital
Grimbacher, Bodo
United Kingdom, London
University College London
Sauer, Martin
Germany, Hannover
Hannover Medical School
Sykora, Karl Walter
Germany, Hannover
Hannover Medical School
Koletzko, Sibylle
Germany, Munich
Klinikum Der Universität München
Klein, Christoph A.
Germany, Hannover
Hannover Medical School
Germany, Munich
Klinikum Der Universität München
Statistics
Citations: 400
Authors: 35
Affiliations: 19
Identifiers
Doi:
10.1053/j.gastro.2012.04.045
ISSN:
00165085
e-ISSN:
15280012
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study