Wada Taizo, Kanegane Hirokazu, Ohta Kazuhide, Katoh Fumiyo, Imamura Toshihiko, Nakazawa Yozo, Miyashita Ritsuko, Hara Junichi, Hamamoto Kazuko, Yang Xi, Filipovich Alexandra H, Marsh Rebecca A, Yachie Akihiro
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Cytokine. 2014 Jan;65(1):74-8. doi: 10.1016/j.cyto.2013.09.007. Epub 2013 Sep 29.
X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency.
X连锁淋巴增殖综合征（XLP）是一种罕见的原发性免疫缺陷病，其特征是对爱泼斯坦-巴尔病毒感染的易感性增加。1型XLP由SH2D1A基因突变引起，而X连锁凋亡抑制蛋白（XIAP）由XIAP/BIRC4编码，在2型XLP中发生突变。在XIAP缺乏症中，噬血细胞性淋巴组织细胞增生症（HLH）更频繁地发生且复发很常见。然而，其潜在机制大多仍不清楚。我们描述了10例XIAP缺乏症患者血清样本的细胞因子谱特征。在患有HLH的患者中，白细胞介素（IL）-18的浓度显著升高，并且在从HLH恢复后仍保持高水平，尽管其他促炎细胞因子的水平接近正常范围。对两名患者的纵向检查表明，在每次HLH发作期间IL-18水平都显著升高。这些发现可能提示在XIAP缺乏症中HLH易感性与高血清IL-18水平之间的关联。
