CAJ | 학술논문

目的：分析EB病毒相关性噬血性淋巴组织细胞增生症（ EBV-HLH）患儿的临床特征及其相关基因缺陷情况。方法于2011年5月至2012年9月收集就诊于首都儿科研究所的EBV-HLH患儿的临床资料16例，男女各8例，年龄1岁2个月至13岁7个月，中位年龄2岁9个月。采用基因测序方法检测HLH相关基因穿孔素（PRF1）基因、UNC13同源蛋白4（UNC13D）基因、突触融合蛋白11（STX11）基因、突触融合蛋白结合蛋白2（STXBP2）基因、SH2结构域1A（SH2D1A）基因及X连锁凋亡抑制蛋白（ XIAP）基因突变。根据HLH基因检测的结果，分析HLH相关基因阳性病例（阳性组）和阴性病例（阴性组）的临床特点及治疗转归。结果16例患儿中有7例患儿能检测出阳性基因，其中，有5例次PRF1、3例次UNC13D、1例次STXBP2、1例次SH2D1A，其中1例患儿同时存在PRF1、UNC13D的突变。 HLH相关基因阳性组（n＝7）和阴性组（n＝9）在性别、年龄、发病年龄初诊时病程间无差异，在临床特征、严重程度、疾病进展速度、EB病毒载量、EBV-DNA持续阳性时间、治疗及转归上差异均无统计学意义（均P＞0.05）。结论 EBV-HLH患儿中，有相当部分患儿存在基因缺陷，且HLH基因缺陷可能不影响EBV-HLH患儿的临床特征及治疗。
목적：분석EB병독상관성서혈성림파조직세포증생증（ EBV-HLH）환인적림상특정급기상관기인결함정황。방법우2011년5월지2012년9월수집취진우수도인과연구소적EBV-HLH환인적림상자료16례，남녀각8례，년령1세2개월지13세7개월，중위년령2세9개월。채용기인측서방법검측HLH상관기인천공소（PRF1）기인、UNC13동원단백4（UNC13D）기인、돌촉융합단백11（STX11）기인、돌촉융합단백결합단백2（STXBP2）기인、SH2결구역1A（SH2D1A）기인급X련쇄조망억제단백（ XIAP）기인돌변。근거HLH기인검측적결과，분석HLH상관기인양성병례（양성조）화음성병례（음성조）적림상특점급치료전귀。결과16례환인중유7례환인능검측출양성기인，기중，유5례차PRF1、3례차UNC13D、1례차STXBP2、1례차SH2D1A，기중1례환인동시존재PRF1、UNC13D적돌변。 HLH상관기인양성조（n＝7）화음성조（n＝9）재성별、년령、발병년령초진시병정간무차이，재림상특정、엄중정도、질병진전속도、EB병독재량、EBV-DNA지속양성시간、치료급전귀상차이균무통계학의의（균P＞0.05）。결론 EBV-HLH환인중，유상당부분환인존재기인결함，차HLH기인결함가능불영향EBV-HLH환인적림상특정급치료。
Objectives To study the clinical features and gene mutations of EBV-HLH in Chinese children.Methods Sixteen pediatric patients with Epstein-Barr virus-associated HLH were enrolled the study from May 2011 to September 2012, who were admitted to Capital Institute of Pediatrics.All patients′clinical features were recorded and their nucleotide sequences of all exons and their flanking intronic sequences of perforin (PRF1)gene, protein unc-13 homolog D (UNC13D)gene,two fusion protein genes of syntaxin 11 (STX11)gene, synaptic binding protein 2 (STXBP2) gene, SH2 domain 1A (SH2D1A)gene, and the X-linked inhibitor of apoptosis protein ( XIAP ) gene were amplified by PCR followed by direct sequencing.Based on HLH gene detection results , all patients divided into the positive and negative gene EBV-HLH subgroups.Statistical analysis was conducted using SPSS 11.5 software.Results Seven of sixteen pediatric patients with EBV-HLH were identified with heterozygous , hemizygous , and homozygous mutations in PRF1, UNC13D, STXBP2, and SH2D1A.No significant differences were found on the gender , age, illness duration, EBV load, the positive duration of EBV-DNA, lab results, clinical symptoms, treatment, and the outcome between the HLH gene positive and negative subgroups ( P >0.05 ). Conclusions A considerable EBV-HLH pediatric patients have genetic defects , and HLH gene defects may not affect the clinical features and treatment of EBV-HLH pediatric patients.