Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy

Gastroenterology. 2012 Aug;143(2):347-55. doi: 10.1053/j.gastro.2012.04.045. Epub 2012 Apr 28.


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Blotting, Western
  • Cohort Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Markers
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Inflammatory Bowel Diseases* / diagnosis
  • Inflammatory Bowel Diseases* / genetics
  • Inflammatory Bowel Diseases* / surgery
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics*
  • Interleukin-10 Receptor alpha Subunit / deficiency
  • Interleukin-10 Receptor alpha Subunit / genetics*
  • Interleukin-10 Receptor beta Subunit / deficiency
  • Interleukin-10 Receptor beta Subunit / genetics*
  • Male
  • Mutation
  • Sequence Analysis, DNA
  • Treatment Outcome


  • Genetic Markers
  • Interleukin-10 Receptor alpha Subunit
  • Interleukin-10 Receptor beta Subunit
  • Interleukin-10