TYK2基因突变致原发性免疫缺陷病1例并文献复习

TYK 2 gene mutations in primary immunodeficiency disease:a case report and literature review

目的 探讨酪氨酸激酶2(TYK2)基因突变致原发性免疫缺陷病(PID)的临床特征、免疫表型、基因突变位点及诊治情况。方法 回顾性分析1例Tyk2基因突变致PID患儿的临床资料、分子遗传学检测结果及治疗情况,并对相关文献进行复习。结果 患儿女,1岁8个月,临床表现为出生后反复肺部感染、湿疹、卡介苗相关并发症;基因检测显示TYK2基因呈复合杂合突变(c.209_delGCTT;p.C70Sfs21/c.1507C>T;p.R503X);经抗感染等治疗,患儿病情好转出院,出院后定期输注人免疫球蛋白。共检索到相关文献11篇,共报道了18例TYK2基因突变致PID患者;TYK2基因突变患者的主要临床表型为胞内菌(尤其是分枝杆菌)感染和(或)病毒感染;免疫学特点为淋巴细胞数量和免疫球蛋白基本正常,但是存在多种细胞因子信号缺陷;TYK2基因突变致PID患者可伴或不伴血清IgE水平升高;常规抗感染治疗方案对大多数患儿有效,部分患儿需抗分枝杆菌治疗。结论 患者有反复细菌感染(尤其是胞内菌)、病毒感染、湿疹或特异性皮炎发作、伴或不伴血清IgE水平升高时,需考虑TYK2基因突变所致PID的可能,基因测序技术有助于该病的早期诊断。

Objective To investigate the clinical features,immunophenotype,gene mutation sites,and diagnosis and treatment of primary immunodeficiency disease(PID) caused by tyrosine kinase 2(TYK2) gene mutation.Methods The clinical data,molecular genetic test results,and treatment of a child with PID caused by Tyk2 gene mutations were retrospectively analyzed,and a review of the relevant literature was conducted.Results The patient was a 1-year and8-month-old girl,who suffered from repeated pulmonary infection,eczema,and BCG-related complications after birth.The genetic test revealed compound heterozygous mutations in the TYK2(c.209_(d)elGCTT;p.C70 Sfs21/c.1507 C>T;p.R503 X).After anti-infection therapy,the patient improved and was discharged from the hospital,and human immunoglobulin was infused regularly after discharge.A total of 11 relevant literatures were retrieved,and 18 patients with PID caused by TYK2 gene mutation were reported.The main clinical phenotype of patients with TYK2 gene mutation was intracellular bacterial(especially mycobacterial) infection and/or viral infection.Immunologically,the number of lymphocytes and immunoglobulins were basically normal,but there were multiple cytokine signaling defects.TYK2 gene mutation caused elevated serum IgE in some PID patients.Conventional anti-infective regimens were effective for most of the children,and some children required anti-mycobacterial therapy.Conclusions When the patient suffers from repeated bacterial infection(especially intracellular bacteria),viral infection,eczema or atopic dermatitis,with or without elevated serum IgE,the possibility of PID caused by TYK2 gene mutation should be considered.Gene sequence analysis can assist in early diagnosis.