Skip to content


  • Invited lecture presentation
  • Open Access

Early-onset inflammatory bowel disease caused by mutant IL10 receptor

  • 1,
  • 2,
  • 2,
  • 3,
  • 3,
  • 2,
  • 1,
  • 2,
  • 2,
  • 2,
  • 2,
  • 4,
  • 2,
  • 2,
  • 5,
  • 6,
  • 7,
  • 1,
  • 8,
  • 9,
  • 6,
  • 10,
  • 11,
  • 12,
  • 13,
  • 14,
  • 1 and
  • 2
Contributed equally
Journal of Translational Medicine20108 (Suppl 1) :I12

  • Published:


  • Inflammatory Bowel Disease
  • Peripheral Blood Mononuclear Cell
  • Hematopoietic Stem Cell Transplant
  • IL10 Receptor
  • Homozygous Mutation


The molecular etiology of inflammatory bowel diseases (IBD) is largely unknown.


We performed genetic linkage analysis and candidate gene sequencing in two unrelated consanguineous families with children affected by early-onset IBD. We screened six additional patients for mutations in two candidate genes and carried out functional assays in patients’ peripheral blood mononuclear cells. We treated one patient with an allogeneic hematopoietic stem cell transplant (HSCT).


We identified three distinct homozygous mutations in the genes IL10RA and IL10RB, encoding the IL10R1 and IL10R2 proteins, respectively (which form a heteromer to make up the interleukin-10 receptor) in four of nine patients with early-onset colitis. The mutations abrogate IL10-induced signaling, as demonstrated by deficient STAT3 phosphorylation upon IL10 stimulation. Consistent with this observation is the increased secretion of TNFα and other proinflammatory cytokines from peripheral blood mononuclear cells from IL10R-deficient patients, suggesting that IL10-dependent “negative feedback” regulation is disrupted in these cells. One patient was successfully treated by an allogeneic HSCT.


Mutations in genes encoding the IL10R subunit proteins cause human enterocolitis, involving hyperinflammatory immune responses in the intestine. Allogeneic HSCT may offer a cure for IL10 receptor deficiency.


Authors’ Affiliations

Dept. of Immunology, Royal Free Hospital and University College London, London, UK
Dept. of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany
National Center for Biotechnology Information, NIH, DHHS, Bethesda, MD, USA
Dept. of Hematology/Oncology, Core Facility II Genomics, Freiburg University Medical Center, Freiburg, Germany
Dept. of Pathology, Hannover Medical School, Hannover, Germany
Dr. von Hauner'sches Kinderspital, Ludwig-Maximilian University, Munich, Germany
Dept. of Pediatric Surgery, Hannover Medical School, Hannover, Germany
Dept. of Pediatric Pulmonology, Hannover Medical School, Hannover, Germany
Dept. of Rheumatology and Clinical Immunology, University Hospital Freiburg, Freiburg, Germany
Dept. of Paediatric Gastroenterology, Great Ormond Street Hospital, University College London, London, UK
Dept. of Medicine, University College London, London, UK
Dept. of Pediatrics, HELIOS Hospital Erfurt, Erfurt, Germany
Dept. of Pediatrics, St.-Marien-Hospital Bonn, Bonn, Germany
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA


© Grimbacher and Klein; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.