Department of Pediatrics, Graduate School of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
J Clin Immunol. 2012 Jun;32(3):411-20. doi: 10.1007/s10875-011-9638-z. Epub 2012 Jan 8.
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.
X 连锁凋亡抑制蛋白（XIAP）缺陷症由 XIAP/BIRC4 基因突变引起，是一种遗传性免疫缺陷病，被归类为 X 连锁淋巴组织增生综合征 2 型。该病主要见于常伴有 EBV 感染的噬血细胞性淋巴组织细胞增生症（HLH）患者。我们描述了来自 6 个无亲缘关系的家庭的 9 名日本 XIAP 缺陷症患者，研究了 XIAP 蛋白表达、XIAP 基因分析、固有自然杀伤 T（iNKT）细胞计数以及 CD8（+）同种抗原特异性细胞毒性 T 淋巴细胞的细胞毒性活性。9 名患者中，8 名患者在婴儿期或幼儿期出现症状。5 名患者表现为复发性 HLH，其中 1 名病情严重，在接受脐带血移植后死亡。1 名患者出现结肠炎，另一名患者的舅舅也出现结肠炎，在被诊断为 XIAP 缺陷症之前，他在 4 岁时死于结肠炎。有趣的是，一名 17 岁的患者无症状，而他的弟弟则患有复发性 HLH 和 EBV 感染。8 名患者中有 7 名表现出 XIAP 蛋白表达减少。与年龄匹配的健康对照组相比，XIAP 缺陷症患者的 iNKT 细胞显著减少。我们日本队列的这些结果与之前的研究一致，证实了 XIAP 缺陷症的临床特征。
