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http://purl.uniprot.org/citations/19890111http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19890111http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19890111http://www.w3.org/2000/01/rdf-schema#comment"

Background

The molecular cause of inflammatory bowel disease is largely unknown.

Methods

We performed genetic-linkage analysis and candidate-gene sequencing on samples from two unrelated consanguineous families with children who were affected by early-onset inflammatory bowel disease. We screened six additional patients with early-onset colitis for mutations in two candidate genes and carried out functional assays in patients' peripheral-blood mononuclear cells. We performed an allogeneic hematopoietic stem-cell transplantation in one patient.

Results

In four of nine patients with early-onset colitis, we identified three distinct homozygous mutations in genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively, which form a heterotetramer to make up the interleukin-10 receptor. The mutations abrogate interleukin-10-induced signaling, as shown by deficient STAT3 (signal transducer and activator of transcription 3) phosphorylation on stimulation with interleukin-10. Consistent with this observation was the increased secretion of tumor necrosis factor alpha and other proinflammatory cytokines from peripheral-blood mononuclear cells from patients who were deficient in IL10R subunit proteins, suggesting that interleukin-10-dependent "negative feedback" regulation is disrupted in these cells. The allogeneic stem-cell transplantation performed in one patient was successful.

Conclusions

Mutations in genes encoding the IL10R subunit proteins were found in patients with early-onset enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic stem-cell transplantation resulted in disease remission in one patient."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.org/dc/terms/identifier"doi:10.1056/nejmoa0907206"xsd:string
http://purl.uniprot.org/citations/19890111http://purl.org/dc/terms/identifier"doi:10.1056/nejmoa0907206"xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Baumann U."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Baumann U."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Klein C."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Klein C."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Shah N."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Shah N."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Sauer M."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Sauer M."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Koletzko S."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Koletzko S."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Lacher M."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Lacher M."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Schaffer A.A."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Schaffer A.A."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Snapper S.B."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Snapper S.B."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Grimbacher B."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Grimbacher B."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Pfeifer D."xsd:string
http://purl.uniprot.org/citations/19890111http://purl.uniprot.org/core/author"Pfeifer D."xsd:string
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