; Güngör, Tayfun ; Enninger, Axel ; Koda, Yu Kar Ling ; Guariso, Graziella
; Weiss, Batia ; Corbacioglu, Selim ; Socha, Piotr
; Uslu, Nuray ; Metin, Ayse ; Wahbeh, Ghassan T. ; Husain, Khalid ; Ramadan, Dina ; Al–Herz, Waleed ; Grimbacher, Bodo ; Sauer, Martin ; Sykora, Karl–Walter ; Koletzko, Sibylle ; Klein, Christoph | Dokumentenart: | Artikel | ||||
|---|---|---|---|---|---|
| Titel eines Journals oder einer Zeitschrift: | Gastroenterology | ||||
| Verlag: | W B SAUNDERS CO-ELSEVIER INC | ||||
| Ort der Veröffentlichung: | PHILADELPHIA | ||||
| Band: | 143 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 2 | ||||
| Seitenbereich: | S. 347-355 | ||||
| Datum: | 2012 | ||||
| Institutionen: | Medizin > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation | ||||
| Identifikationsnummer: |
| ||||
| Stichwörter / 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 | ||||
| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status: | Veröffentlicht | ||||
| Begutachtet: | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden: | Ja | ||||
| Dokumenten-ID: | 63530 |
Zusammenfassung
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 ...

Zusammenfassung
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.
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