普通变异型免疫缺陷病临床表型及TACI基因研究

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目的总结普通变异型免疫缺陷病(common variable immunodeficiency,CVID)儿童患者的临床特点,对CVID相关基因进行研究,为临床诊断和治疗提供依据。方法回顾性分析2003年1月至2013年12月在上海交通大学医学院附属上海儿童医学中心和新华医院就诊的53例CVID儿童患者临床资料,探讨其人口学特征、临床表现、免疫学特征、治疗和转归,并对其中22例患儿进行TACI基因测序。结果发病中位年龄为5.34(1~16)岁,诊断延迟的中位时间为5.05(0~17.9)年。反复呼吸道感染为CVID主要表现(79.2%);77.4%患儿合并其他症状,如肝脾肿大、自身免疫性疾病等。56.6%患儿在确诊后未能接受规范静脉输注丙种球蛋白(IVIG)治疗,规范治疗组患反复呼吸道感染例数显著低于未规范治疗组(P<0.05)。6例死亡。多数患儿血清Ig G、Ig A和Ig M三种免疫球蛋白均明显减低,其中血清Ig G水平1.39(0.33~1.93)g/L,Ig A 0.22(0.04~0.87)g/L,Ig M 1.36(0.04~1.44)g/L。CD8+T淋巴细胞的百分比值增高,52.8%患儿CD4/CD8比值倒置。TACI基因测序发现了2种新的突变:Cys100Tyr和Ser165Asn。结论在我国大陆地区,CVID仍未获得临床医师的充分重视,早期诊断和规范IVIG治疗对CVID患儿的预后可产生明显影响。基因突变对CVID患儿发病机制及治疗方向的影响,仍有待进一步研究。 Objective To summarize the clinical features of children with common variable immunodeficiency (CVID) and to study the related genes of CVID, so as to provide the basis for clinical diagnosis and treatment. Methods The clinical data of 53 CVID pediatric patients attending Shanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine and Xinhua Hospital from January 2003 to December 2013 were retrospectively analyzed to investigate their demographic characteristics, clinical manifestations, immunological characteristics, Treatment and prognosis, TACI gene sequencing was performed on 22 of them. Results The median age of onset was 5.34 (range, 1 to 16 years). The median time to diagnosis was 5.05 (ranged from 0 to 17.9) years. Recurrent respiratory tract infection was the main manifestation of CVID (79.2%); 77.4% of children had other symptoms such as hepatosplenomegaly and autoimmune diseases. Fifty-six (56.6%) children did not receive standard IVIG after diagnosis. The number of recurrent respiratory infections in the standard treatment group was significantly lower than that in the non-standard treatment group (P <0.05). 6 died. Serum Ig G levels of 1.39 (0.33-1.93) g / L, Ig A 0.22 (0.04-0.87) g / L, Ig M 1.36 (0.04 ~ 1.44) g / L. The percentage of CD8 + T lymphocytes increased, while the CD4 / CD8 ratio of 52.8% of infants was inverted. TACI gene sequencing found two new mutations: Cys100Tyr and Ser165Asn. Conclusion In China, CVID has not received the full attention of clinicians. Early diagnosis and standardization of IVIG treatment may have a significant impact on the prognosis of children with CVID. Genetic mutations in children with CVID pathogenesis and treatment of impact, remains to be further studied.
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