Clinical and genetic characteristics of XIAP deficiency in Japan.
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.
Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Xi
X
Yang
Hirokazu
H
Kanegane
Naonori
N
Nishida
Toshihiko
T
Imamura
Kazuko
K
Hamamoto
Ritsuko
R
Miyashita
Kohsuke
K
Imai
Shigeaki
S
Nonoyama
Kazunori
K
Sanayama
Akiko
A
Yamaide
Fumiyo
F
Kato
Kozo
K
Nagai
Eiichi
E
Ishii
Menno C
MC
van Zelm
Sylvain
S
Latour
Xiao-Dong
XD
Zhao
Toshio
T
Miyawaki
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018655:Lymphocyte Count; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D055611:Natural Killer T-Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology
D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human