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Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
IL-10R polymorphisms are associated with very-early-onset ulcerative colitis
Christopher J Moran1, Thomas D Walters, Cong-Hui Guo
1Division of Pediatric Gastroenterology, Department of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts, USA.
Inflammatory Bowel Diseases
|May 3, 2012
Summary
Interleukin-10 receptor A (IL10RA) gene polymorphisms increase the risk of very-early-onset ulcerative colitis (VEO-UC). A novel IL10RA mutation caused infantile-onset inflammatory bowel disease (IBD), expanding the known IL10RA-associated phenotypes.
Area of Science:
- Genetics
- Immunology
- Gastroenterology
Background:
- Interleukin-10 (IL-10) is crucial for restricting intestinal inflammation.
- IL-10 pathway gene polymorphisms are implicated in inflammatory bowel disease (IBD).
- Mutations in IL-10 and IL-10 receptor (IL-10R) genes are linked to severe infantile-onset IBD.
Observation:
- This study investigated the association of IL-10 receptor (IL-10R) polymorphisms with early-onset IBD (EO-IBD) and very-early-onset IBD (VEO-IBD).
- A novel homozygous splice-site mutation (P206X) in IL10RA was identified in an infant with IBD, leading to IL-10 insensitivity.
- Candidate-gene analysis of IL10RA and IL10RB was performed in discovery and validation cohorts.
Findings:
- Five IL10RA polymorphisms were associated with ulcerative colitis (UC), and two IL10RB polymorphisms with Crohn's disease (CD).
- Two IL10RA single nucleotide polymorphisms (SNPs), rs2228054 and rs2228055, were significantly associated with VEO-UC in both discovery and validation cohorts.
- The identified IL10RA mutation represents the first reported splice-site mutation causing infantile-onset IBD.
Implications:
- IL10RA polymorphisms are confirmed risk factors for VEO-UC.
- The study expands the clinical spectrum of IL10RA-associated conditions to include VEO-UC and severe arthritis.
- Genetic analysis of IL-10R pathway genes is critical for diagnosing and understanding early-onset IBD phenotypes.
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