RARE MUTATION IN AIRE GENE IDENTIFIED IN PATIENT WITH VERY EARLY ONSET IBD

Abstract

<h3>Introduction</h3> The etiology of very early-onset inflammatory bowel disease (VEO IBD) is thought to have a greater likelihood of being due to a monogenic inborn error of immunity than later-onset IBD. <h3>Case Description</h3> We present the case of a 6-year-old female with VEO IBD who was found to have a variant of unknown significance (VUS) in the AIRE gene. She was diagnosed with VEO IBD at 2 years old after she was found to have failure to thrive, diarrhea, and blood in stool. She was initially treated with mesalamine, azathioprine, and steroids, but never went into remission. She does not have history of recurrent infections or other symptoms of autoimmune disease. There is no significant known family history of autoimmune disease. Labs were notable for normal antibody responses to Hep A, Hep B, and VZV vaccines, but low S. pneumoniae titers despite vaccination with Prevnar. She had normal T and B-cell counts, including T-cell subsets, and a normal oxidative burst test. Invitae PID panel was notable for a rare heterozygous VUS in AIRE gene. Given mutations in AIRE gene are associated with the autoimmune disease APECED, plan was made to test family for VUS in AIRE and evaluate for immunologic defects seen in AIRE, such as low Tregs and IL-17, as well as elevated ANA and autoantibodies to GAD65 and thyroid. <h3>Discussion</h3> While various organs are affected in APECED, the intestinal tract is not usually affected. Nonetheless, given early onset of IBD, strong suspicion remains for monogenic disorder, either in AIRE or other genes.