Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2
Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2
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DOI：
10.1182/blood-2010-05-282541
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发表时间：
2010-10-14
期刊：
影响因子：
20.3
通讯作者：
Henter, Jan-Inge
中科院分区：
文献类型：
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作者：
Meeths, Marie;Entesarian, Miriam;Henter, Jan-Inge
噬血细胞淋巴组织细胞增多症是一种常见的致命性高炎症综合征，以发热、肝脾肿大、细胞减少为特征，有时还伴有吞噬血细胞。在这里，我们描述了编码Munc18-2的STXBP2突变患者的自然杀伤(NK)细胞的突变分析、临床表现和功能分析，最近与家族性HLH5型有关。在这里研究的11人的疾病严重程度是高度可变的，因此，诊断的年龄从2个月到17岁。值得注意的是，除了家族性HLH(FHL)的典型表现外，约三分之一的患者的临床表现包括结肠炎、出血性疾病和低丙种球蛋白血症。实验室分析显示NK细胞脱颗粒和细胞毒能力受损。IL-2体外刺激淋巴细胞可挽救NK细胞相关的功能缺陷。总之，家族性HLH5型与一系列临床症状有关，这可能反映了Munc18-2在细胞毒性淋巴细胞以外的细胞中的表达和功能受损。因此，STXBP2基因突变也应该被考虑用于临床表现不同于通常与HLH相关的患者。(《血色》2010；116(15)：2635-2643)
Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell-associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH. (Blood.2010;116(15):2635-2643)