难治性病毒感染和原发噬血细胞性淋巴组织细胞增多症相关基因突变研究
난치성병독감염화원발서혈세포성림파조직세포증다증상관기인돌변연구
The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistocytosis
  • 万方数据
    中华内科杂志 중화내과잡지
    CHINESE JOURNAL OF INTERNAL MEDICINE
    2011年 4期 280-283 ,共4页

    童春容%刘红星%谢建军%王芳%蔡鹏%王卉%朱娟%滕文%张弦%杨君芳%张雅丽%费新红%赵杰%殷宇明%吴彤%王静波%孙媛%刘嵘%师晓东%陆道培

    동춘용%류홍성%사건군%왕방%채붕%왕훼%주연%등문%장현%양군방%장아려%비신홍%조걸%은우명%오동%왕정파%손원%류영%사효동%륙도배

    淋巴组织细胞增多症,嗜血细胞性%病毒性疾病%突变%淋巴瘤%EB病毒 淋巴組織細胞增多癥,嗜血細胞性%病毒性疾病%突變%淋巴瘤%EB病毒
    림파조직세포증다증,기혈세포성%병독성질병%돌변%림파류%EB병독
    Lymphohistocytosis,hemophagocytic%Virus diseases%Mutation%Lymphoma%Epstein-Barr virus
    目的 研究难治性病毒感染或噬血细胞性淋巴组织细胞增多症(HLH)中免疫基因突变的发生率、类型及其临床特征.方法 采用基因测序方法 检测难治性病毒感染或HLH患者是否有原发性HLH相关的PRF1、UNC13D、STX11、STXBP2、SH2D1A和XIAP基因突变,并追踪其临床特点及转归.结果 共25例难治性病毒感染性疾病或HLH患者接受了基因突变筛查,其中13例检测到上述基因突变:PRF1突变6例,UNC13D突变3例,STX11、STXBP2、SH2D1A、XIAP突变各1例;其中6例起病表现为病毒相关性HLH,1例为原因不明HLH,4例为慢性活动性EB病毒(EBV)感染(CAEBV),2例为EBV相关性淋巴瘤.12例未检测出基因突变的患者中,4例为EBV相关HLH,其中1例发展为外周T细胞淋巴瘤,另8例为CAEBV.结论 原发性HLH相关免疫基因突变是难治性病毒感染或HLH的重要原因,大部分表现为HLH,部分患者以CAEBV或EBV相关淋巴瘤起病.基因检测是明确此类疾病诊断的有力证据.
    목적 연구난치성병독감염혹서혈세포성림파조직세포증다증(HLH)중면역기인돌변적발생솔、류형급기림상특정.방법 채용기인측서방법 검측난치성병독감염혹HLH환자시부유원발성HLH상관적PRF1、UNC13D、STX11、STXBP2、SH2D1A화XIAP기인돌변,병추종기림상특점급전귀.결과 공25례난치성병독감염성질병혹HLH환자접수료기인돌변사사,기중13례검측도상술기인돌변:PRF1돌변6례,UNC13D돌변3례,STX11、STXBP2、SH2D1A、XIAP돌변각1례;기중6례기병표현위병독상관성HLH,1례위원인불명HLH,4례위만성활동성EB병독(EBV)감염(CAEBV),2례위EBV상관성림파류.12례미검측출기인돌변적환자중,4례위EBV상관HLH,기중1례발전위외주T세포림파류,령8례위CAEBV.결론 원발성HLH상관면역기인돌변시난치성병독감염혹HLH적중요원인,대부분표현위HLH,부분환자이CAEBV혹EBV상관림파류기병.기인검측시명학차류질병진단적유력증거.
    Objective To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. Methods From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. Results Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11,XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH( EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH),1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t ( 15; 17 ) (q22; q25 ) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. Conclusions Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH,some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.
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