Clinical and genetic characteristics of XIAP deficiency in Japan

Xi Yang, Hirokazu Kanegane, Naonori Nishida, Toshihiko Imamura, Kazuko Hamamoto, Ritsuko Miyashita, Kohsuke Imai, Shigeaki Nonoyama, Kazunori Sanayama, Akiko Yamaide, Fumiyo Kato, Kozo Nagai, Eiichi Ishii, Menno C. Van Zelm, Sylvain Latour, Xiao Dong Zhao, Toshio Miyawaki

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Deficiency of X-linked inhibitor of apoptosis (XIAP) caused by XIAP/BIRC4 gene mutations is an inherited immune defect recognized as X-linked lymphoproliferative syndrome type 2. This disease is mainly observed in patients with hemophagocytic lymphohistiocytosis (HLH) often associated with Epstein-Barr virus infection. We described nine Japanese patients from six unrelated families with XIAP deficiency and studied XIAP protein expression, XIAP gene analysis, invariant natural killer T (iNKT) cell counts, and the cytotoxic activity of CD8 + alloantigen-specific cytotoxic T lymphocytes. Of the nine patients, eight patients presented with symptoms in infancy or early childhood. Five patients presented with recurrent HLH, one of whom had severe HLH and died after cord blood transplantation. One patient presented with colitis, as did another patient's maternal uncle, who died of colitis at 4 years of age prior to diagnosis with XIAP deficiency. Interestingly, a 17-year-old patient was asymptomatic, while his younger brother suffered from recurrent HLH and EBV infection. Seven out of eight patients showed decreased XIAP protein expression. iNKT cells from patients with XIAP deficiency were significantly decreased as compared with age-matched healthy controls. These results in our Japanese cohort are compatible with previous studies, confirming the clinical characteristics of XIAP deficiency.

Original languageEnglish
Pages (from-to)411-420
Number of pages10
JournalJournal of Clinical Immunology
Issue number3
Publication statusPublished - Jun 2012
Externally publishedYes


  • Epstein-Barr virus
  • hemophagocytic lymphohistiocytosis
  • invariant natural killer T cell
  • X-linked inhibitor of apoptosis
  • X-linked lymphoproliferative syndrome

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