摘要
目的了解我国小儿噬血细胞综合征(HLH)的发病情况和治疗效果,并开展HLH的穿孔素(perforin)基因研究。方法研究对象为符合国际组织细胞协会HLH-2004诊断标准的18例患儿,分析患儿起病时及治疗后的临床资料。用流式细胞仪和基因测序法检测患儿的穿孔素基因。结果流式细胞仪检测发现1例患儿的穿孔素在CD8+T细胞和NK细胞中的表达几乎完全缺如,而且基因测序发现该患儿的穿孔素基因存在错义突变(G47C),确诊为原发性HLH。14例接受HLH-2004治疗,随访时间2周～39个月,临床缓解4例,复发4例,持续活动4例,失访2例。共死亡7例。结论HLH-2004是诊断和治疗小儿HLH的有效方案,提高生存率需积极开展造血干细胞移植。为鉴别原发性和继发性HLH应进行相关基因检测。
Objective Hemophagoeytic lymphohistiocytosis （HLH） is a pediatric disease with high mortality. In China, there are few studies on long-term follow-up based on standard diagnosis and treatment of HLH, and the reports on genetic diagnosis of HLH are absent. This study aimed to explore the therapeutic effect of HLH in children in China diagnosed and treated by HLH-2004 protocol announced by Histioeyte Society and to conduct the pefforin gene research in HLH. Methods Eighteen children aged 9 months to 10 years （12 males and 6 females） based on the diagnostic eriteria of HLH-2004 were enrolled. Their elinical materials were collected and analyzed at the onset of HLH and after therapy. The HLH-ehildren＇s pefforin genes were studied by flow eytometry and gene sequencing. Results Pefforin gene detection： the flow eytometry assay found that the expressions of perforin in CD8^＋T cell and NK cell of one patient were nearly absent, furthermore a missense mutation （G47C） of pefforin gene was identified in this patient through gene sequencing, thus the primary/familial HLH was diagnosed. Therapeutic effect： 14 cases received HLH-2004 therapy, follow-up time ranged from 2 weeks to 39 months. Hemopoietic stem cell transplantation did not adopt in this research yet. Four cases achieved clinical remission, while 4 cases suffered from reactivations and continuous activations respectively, and 2 cases dropped off. Totally 7 cases died. Conclusions HLH-2004 protocol has an effect on the diagnosis and treatment of HLH in children. Hemopoietie stem cell transplantation should be conducted actively so as to increase the survival rate. Genetic study is a good way to differentiate primary HLH from secondary HLH.
出处
《临床儿科杂志》
CAS
CSCD
北大核心
2009年第8期718-722,共5页
Journal of Clinical Pediatrics
基金
复旦大学青年科学基金项目资助(No.JKF156002)
关键词
噬血细胞综合征
儿童
基因诊断
穿孔素
hemophagoeytie lymphohistiocytosis
children
genetic diagnosis
perforin
