Intestinal Research (Jan 2022)

A case of autoimmune enteropathy with CTLA4 haploinsufficiency

  • Haruka Miyazaki,
  • Namiko Hoshi,
  • Michitaka Kohashi,
  • Eri Tokunaga,
  • Yuna Ku,
  • Haruka Takenaka,
  • Makoto Ooi,
  • Nobuyuki Yamamoto,
  • Suguru Uemura,
  • Noriyuki Nishimura,
  • Kazumoto Iijima,
  • Keisuke Jimbo,
  • Tsubasa Okano,
  • Akihiro Hoshino,
  • Kohsuke Imai,
  • Hirokazu Kanegane,
  • Ichiro Kobayashi,
  • Yuzo Kodama

DOI
https://doi.org/10.5217/ir.2020.00041
Journal volume & issue
Vol. 20, no. 1
pp. 144 – 149

Abstract

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Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.

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