干扰素γ受体l缺陷的临床功能及基因分析-第三军医大学学报.docVIP

干扰素γ受体1缺陷患儿的临床特征及功能、基因分析 胥焕1，蒋利萍*1，邢超1，刘霞1，肖剑文2 （1重庆医科大学附属儿童医院临床免疫研究室，儿童发育疾病研究教育部重点实验室，儿科学重庆市重点实验室，重庆市儿童发育重大疾病诊治与预防国际科技合作基地，重庆，400014；2重庆医科大学附属儿童医院血液肿瘤科，重庆，400014） [摘要] 目的：探讨1例疑似孟德尔遗传易感分枝杆菌病（Mendelian susceptibility to mycobacterial disease，MSMD）患儿的临床特征、检测IL-12/23-IFN-γ通路的完整性，并进行干扰素γ受体l(IFNGR1)基因分析。方法：根据患儿的临床表现及常规的免疫学筛查试验排除常见原发性免疫缺陷病，Q-RT-PCR在mRNA水平检测患儿及健康对照者IL-12/23-IFN-γ通路的完整性，通过PCR及RT-PCR分别对患儿及其父母的IFNGR1基因进行扩增并测序。结果：患儿有播散性卡介苗（BCG）病及全身多系统损害的表现。患儿全血经BCG和IFN-γ共同刺激48h后IL-12B的表达水平与单独BCG刺激后比较明显降低；基因测序发现患儿IFNGR1第6外显子818-821位杂合缺失4个碱基（c.818-821delTTAA），使第276位脯氨酸突变为终止密码（p.Asn274fsX276），父母此位点正常。结论：Q-RT-PCR检测IL-12/23-IFN-γ通路完整性是一种有效的筛查MSMD的手段；IFNGR1突变是引起本例患儿发生播散性BCG病及全身多系统病变的根本原因。 [关键词] 干扰素γ受体l缺陷；孟德尔遗传易感分枝杆菌病；卡介苗 [中图分类号] R725.9 Clinical features, function and molecular analysis of one child with IFN-γ receptor 1 deficiency Xu Huan1，Jiang Liping1*，Xing Chao1，Liu Xia1，Xiao Jianwen2 (1 Clinical Immunology Laboratory, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, 2 Department of Hematology/Oncology, Childrens Hospital of Chongqing Medical University, Chongqing, 400014, China) [Abstract] Objective To explore the clinical feature, detect the function of the IL-12/23-IFN-γ axis and identify the IFNGR1 gene mutation in a child with suspected Mendelian susceptibility to mycobacterial disease (MSMD). Methods Firstly, we ruled out the common primary immunodeficiency disease (PID) based on the clinical manifestation and screening tests of immune function, and then detected the integrity of the IL-12/23-IFN-γ axis by Q-RT-PCR. IFNGR1 gene was sequenced according to the results of Q-RT-PCR. Results The child suffered from disseminated BCG disease and multi-system lesions. The production of IL-12B in response to BCG plus IFN-γ was reduced compared with stimula