CIITA基因突变所致MHCⅡ分子缺陷病2例临床分析并文献复习

MHC class Ⅱ-deficiency caused by CIITA gene mutation:A report of two cases and literature review

目的总结MHCⅡ分子缺陷患儿的临床表现、诊断方法和治疗,提高对该病的认识。方法回顾性分析2012年8月、2016年1月复旦大学附属儿科医院确诊的2例MHCⅡ分子缺陷患儿临床资料、免疫功能、蛋白表达及基因分析结果,结合以往文献分析疾病诊断方法及治疗。结果 2例患儿均为男性,起病年龄分别为4岁、2个月,确诊年龄分别为8岁、3个月。2例均有肺部感染。1例伴腹泻,1例卡介苗接种后同侧腋下淋巴结切开引流。2例均对真菌、病毒、细菌易感,经广谱抗生素及抗真菌药物治疗后,仍因感染死亡。死亡年龄分别为8岁、3个月。1例粒细胞减少,2例均贫血,CD4+T细胞数均显著减少,1例免疫球蛋白显著减少。1例活化T细胞表面HLA-DR蛋白表达较正常对照明显减少。CIITA基因分析结果示:例1为复合杂合突变,第7个外显子c.531C>A(来源于父亲),第11个外显子c.2408C>A(来源于母亲)。例2为纯合无义突变,第11个外显子c.1161G>A。2例均因感染未行造血干细胞移植。结论 MHCⅡ分子缺陷生后早期起病,对各种病原易感,常规抗感染治疗疗效不佳,早期诊断、早期进行造血干细胞移植是目前患儿存活的惟一方法,基因治疗仍处于研究阶段。

Objective To summarize and analyze the clinical characteristics, diagnosis and treatment of children with Major Histocompatibility Complex Class Ⅱ （MHC-Ⅱ ） deficiency, in order to promote the awareness of this disease. Methods Retrospectively analyze the clinical features, immunological functions, protein expressions and genetic profiles of 2 children with MHC- Ⅱ deficiency identified from Children＇ s Hospital of Fudan University, and discuss the method of diagnosis and treatment by reviewing related literatures. Results （ 1 ） Both of the patients were male and had a history of recurrent infection, and the age of onset was 4 years and 2 months, respectively ; the age of diagnosis was 8 years and 3 months.Both had pulmonary infection; one had diarrhea and one was infected after BCG vaccination. Both were susceptible to fungi and virus, and even under the treatment of broad spectrum antibiotics and antifungal drugs, they were both dead from severe infection at the age of 8y and 3m, respectively. （2）One had neutropenia, two developed anemia, one had hypogammaglobulinemia, and both had severe CD4 T-cell lymphopenia. （3）Genetic analysis of CIITA showed that P1 had compound heterozygous mutations, with c.531C 〉 A mutation in exon 7 （inherited from father） and c.2408C 〉 A mutation in exon 11 （inherited from mother） ;P2 carried a homozygous nonsense mutation, with c.1161G 〉 A in exon 11 as well. （4）Due to severe infection, both patients failed to undergo the HSCT. Conclusion Patients with MHC Ⅱ deficiency usually experience early onset and are susceptible to various pathogens. Conventional anti-infection treatment is not effective for them. Early diagnosis and HSCT is the only effective way for them to survive ; gene therapy is still in the research stage.