核因子κB2基因突变致普通变异型免疫缺陷病一例并文献复习  

De novo NFκB2 gene mutation associated common variable immunodeficiency

作　　者：罗明珠[1] 徐涛 薛秀红[1] 王艳平[1] 吴沛霖[1] 陈学梅[1] 唐雪梅[1] 赵晓东[1] 张志勇[1] Luo Mingzhu;Xu Tao;Xue Xiuhong;Wang Yanping;Wu Peilin;Chen Xuemei;Tang Xuemei;Zhao Xiaodong;Zhang Zhiyong(Department of Rheumatology and Immunology,Children＇s Hospital of Chongqing Medical University,Ministry of Education Key Laboratory of Child Development and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Child Infection and Immunity,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院风湿免疫科儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿童感染免疫重庆市重点实验室,400014

出　　处：《中华儿科杂志》2018年第8期628-632,共5页Chinese Journal of Pediatrics

摘　　要：目的 探讨核因子κB2（NFκB2）基因突变致普通变异型免疫缺陷病（CVID）的临床、免疫学及分子特征.方法 分析2015年12月重庆医科大学附属儿童医院诊治的1例NFκB2基因失功能突变致CVID患儿的临床特点、生化检查、免疫功能、分子特征、治疗及随访,并以“NFκB2”“免疫缺陷”为检索词,检索2013年1月至2017年11月中文数据库及PUBMED数据库进行文献复习.结果 患儿男,1岁2月龄,自生后6月龄起发生下呼吸道感染4次及中耳炎1次;血清免疫球蛋白水平降低：IgG 2.73 g/L,IgA＜0.07 g/L,IgM 0.12 g/L;外周血淋巴细胞精细免疫分型：T细胞比例升高（81.8％）,其中初始CD4＋T细胞比例升高（39.1％）,总B细胞比例正常,但记忆B细胞和浆母细胞比例下降（分别为0.1％和0）,自然杀伤（NK）细胞比例稍下降（4.13％）;外周血单个核细胞CD4＋T细胞中,调节性T细胞（1.49％）、滤泡辅助T细胞（3.66％）及辅助性T细胞17 （9.65％）比例下降,辅助性T细胞2比例升高（60.9％）;T细胞增殖反应及T细胞抗原受体多样性均未见异常;NK细胞细胞毒功能缺陷;全外显子组测序发现NFκB2基因22号外显子无义突变（c.2557C＞T;p.Arg853X）.免疫印迹检测提示患儿NF-κB2蛋白（p52）表达降低.患儿定期行静脉输注入丙种球蛋白（400-600mg/kg）,肺部感染情况明显好转.文献检索到10篇英文文献,包括国外报道27例和国内报道1例.其中无义突变有12例（5例为增功能突变）、错义突变和移码突变各8例.临床表现以呼吸道感染为主,可发生秃头、砂纸甲等自身免疫现象.15例患儿合并促肾上腺皮质激素（ACTH）缺乏.结论 NF-κB2通路可影响T细胞、B细胞的分化及NK细胞细胞毒功能.临床上以反复感染、低丙种球蛋白血症、记忆B细胞及浆细胞水平低下,尤其是合并ACTH缺乏为主要表现的需警惕NF-κB2缺陷,应尽早行基因检查明确诊断.Objective To investigate the clinical,immunological,and molecular manifestations of nuclear factor kappa-B subunit 2 （NFκB2） gene mutation associated common variable immunodeficiency （CVID）.Methods A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children＇s Hospital of Chongqing Medical University in December 2015.The clinical manifestations,biochemical tests,immunological function,molecular features,treatment,and follow-up of the patient were analyzed.The Chinese and PUBMED databases were searched with the key words ＂NFκB2＂ and＂immune deficiency＂ and related literatures were reviewed.Results The patient had 4 episodes of pneumonias and one otitis media since the age of 6 months.The serum immunoglobulin levels were IgG 2.73 g/L,IgA〈0.07 g/L,and IgM 0.12 g/L.The percentage of peripheral lymphocyte subsets demonstrated increased CD3＋T lymphocyte （81.8%）,increased CD4＋ na（i）ve T cell （39.1%）,normal B cell （14.1%）,low switched memory B and plasmablast B （respectively 0.1% and 0）,and lightly diminished natural killer（NK） cell （4.13%）.Within the peripheral CD4＋T cells,the percentage of regulatory T cells （1.49% （control 4.08%））,T follicular helper （3.66% （control 11.0%））,and T helper 17 （9.65% （control 15.7%）） were decreased,while the percentage of T helper 2 （60.9% （control 46.5%）） was elevated.T lymphocyte proliferative response and T cell receptor repertoire diversity were normal.NK-cell cytotoxic activity was impaired.The whole-exome sequencing harbored a de novo heterozygous nonsense mutation in exon 22 （c.2557C〉T;p.Arg853X） in the C-terminus of NF-κB2.The western blotting confirmed the decreased expression of NF-κB2 （p52） protein.The patient received intravenous immunoglobulin infusion monthly （400-600 mg/kg）,followed by improvement of pulmonary infection.After searching the databases,a total of 28 cases （1 Chinese and 27 non-Chinese） were identified.There were 12 cases of nonsense mu

关 键 词：基因 促肾上腺皮质激素 免疫缺陷综合征 

分 类 号：R725.9[医药卫生—儿科]