Very early-onset inflammatory bowel disease (IBD) in infancy is a different disease entity from adult-onset IBD; one form of interleukin-10 receptor mutations

Abstract

Infantile periods may have stronger genetic influences. Recently, studies on genetic defects in the interleukin-10 (IL-10) signaling pathway have provided new insights into inflammatory bowel disease (IBD). This study is to reveal whether mutations of IL-10 signaling pathway genes contribute to the phenotypes of IBD. Forty children who were diagnosed with IBD below the age of 10 years were enrolled. We sequenced the genes interleukin-10 receptor A (IL-10RA), IL-10RB and IL-10, and analyzed the clinical characteristics of very early-onset IBD (VEO-IBD). In total, 14 out of the 40 children developed their symptoms within 1 year of age. We found mutations in IL-10RA in 7 out of the 40 children (17.5%). All seven children had developed symptoms within the first year of life. Particularly, half of the children with infantile-onset IBD had IL-10RA mutations. None of the remaining 26 children diagnosed above 1 year of age had IL-10RA mutations. No mutations were found in IL-10RB and IL-10. Identified IL-10RA mutations were p.(R101W), p.(Y91C), p.(R262C), p.(R117H) and p.(W69R). IL-10RA mutations were associated with onset of infancy (P<0.001), perianal fistulae (P<0.001), poor response to medical management (P=0.017) and early surgical interventions (P<0.001). VEO-IBD in infancy is phenotypically and genetically different disease entity from adult-onset or older child-onset IBD. It has a strong association with IL-10 receptor gene. We should consider the genotyping of genes of the IL-10 signaling pathway including IL-10RA in patients with VEO-IBD, especially in whom with onset of perianal fistulae and severe colitis.

Genetic association and epistatic interaction of the interleukin-10 signaling pathway in pediatric inflammatory bowel disease

“…Recently, pediatric/VEO IBD has been suggested to be a distinct form of IBD[11,62], and SNPs in IL-10 and IL-10 receptors have been associated with VEO IBD[7-12]. In the present study, we identified IL-10 SNP of rs3024496 to be associated with pediatric IBD; this has not been shown to be associated with adult IBD.…”

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

“…Similarly, Shim et al[22] reported that only seven (50%) of the 14 Korean infants with IO-IBD had mutations in IL10RA. Thus it is likely that IO-IBD represents a heterogeneous group of disorders with the common feature of early-onset severe colitis within the first weeks to months of life[8,9,14,22]. Mutations in IL10 and IL10R may be responsible in a significant proportion of, but not all, young children with IO-IBD.…”

“…Instead the authors found additional compromised signaling in IL22 in a patient with absent IL10RB[14]. Similarly, Shim et al[22] reported that only seven (50%) of the 14 Korean infants with IO-IBD had mutations in IL10RA. Thus it is likely that IO-IBD represents a heterogeneous group of disorders with the common feature of early-onset severe colitis within the first weeks to months of life[8,9,14,22].…”

“…We reported the first case of IO-IBD in an Asian infant due to mutations in the IL10R by using exome sequencing[21]. Subsequently, other authors have also reported early-onset IBD due to mutations in IL-10R[22]. The aims of the present study were to describe the phenotypic characteristics and outcome of IO-colitis in a cohort of Asian children and to define the role of IL10 and IL10R mutations in these patients.…”

IL-10 and IL-10 Receptor Mutations in Very Early Onset Inflammatory Bowel Disease

“…Meanwhile, VEO-IBD cases from Asian countries tend to have higher rate of IL-10/IL-10R mutations. For example, one study from Korea reported that seven of 14 IBD patients (50%) diagnosed within 1 year of age had IL-10RA mutations [20]. The prevalence of IL-10R mutations was also strikingly high in VEO-IBD cases from China.…”