Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy.
Gastroenterology
; 143(2): 347-55, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22549091
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Inflamatórias Intestinais
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Interleucina-10
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Transplante de Células-Tronco Hematopoéticas
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Subunidade alfa de Receptor de Interleucina-10
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Subunidade beta de Receptor de Interleucina-10
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Evaluation_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article