Duplication of the IL2RA locus causes excessive IL-2 signaling and may predispose to very early onset colitis.

ABSTRACT: Single genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including the IL2RA locus, in a 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy. Strikingly, after colectomy while the patient was in clinical remission and without medication, the peripheral blood CD4:CD8 ratio was constitutively high and CD25 expression was increased on circulating effector memory, Foxp3⁺, and Foxp3^neg CD4⁺ T cells compared to healthy controls. This high CD25 expression increased IL-2 signaling, potentiating CD4⁺ T-cell-derived IFNγ secretion after T-cell receptor (TCR) stimulation. Restoring CD25 expression using

SUBMITTER: Joosse ME 

PROVIDER: S-EPMC8379074 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature