Kotlarz, Daniel and Beier, Rita and Murugan, Dhaarini and Diestelhorst, Jana and Jensen, Ole and Boztug, Kaan and Pfeifer, Dietmar and Kreipe, Hans and Pfister, Eva-Doreen and Baumann, Ulrich and Puchalka, Jacek and Bohne, Jens and Egritas, Odul and Dalgic, Buket and Kolho, Kaija-Leena and Sauerbrey, Axel and Buderus, Stephan and Guengoer, Tayfun and Enninger, Axel and Ling Koda, Yu Kar and Guariso, Graziella and Weiss, Batia and Corbacioglu, Selim and Socha, Piotr and Uslu, Nuray and Metin, Ayse and Wahbeh, Ghassan T. and Husain, Khalid and Ramadan, Dina and Al-Herz, Waleed and Grimbacher, Bodo and Sauer, Martin and Sykora, Karl-Walter and Koletzko, Sibylle and Klein, Christoph (2012) Loss of Interleukin-10 Signaling and Infantile Inflammatory Bowel Disease: Implications for Diagnosis and Therapy. GASTROENTEROLOGY, 143 (2). pp. 347-355. ISSN 0016-5085, 1528-0012
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; GENOME-WIDE ASSOCIATION; REFRACTORY CROHNS-DISEASE; NON-HODGKINS-LYMPHOMA; COMPLETE REMISSION; RECEPTOR; PATHOGENESIS; LEUKEMIA; COLITIS; Children; Genetic Defect; Immunodeficiency; Intestinal Inflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2020 08:49 |
| Last Modified: | 11 May 2020 08:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18408 |
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