自身免疫性淋巴增生综合征一例并文献复习  

A case of autoimmune lymphoproliferactive syndrome and literature review

作　　者：刘力[1] 胡坚[1] 马继军[1] 李小洁[1] 李芳芳[1] 李崇巍[1] 

机构地区：[1]天津市儿童医院风湿免疫科,300074

出　　处：《中华儿科杂志》2014年第12期923-926,共4页Chinese Journal of Pediatrics

摘　　要：目的 总结自身免疫性淋巴增生综合征（ALPS）临床特点及诊治要点.方法 对天津市儿童医院风湿免疫科2014年2月20日收治1例ALPS患儿的症状、体征、化验检查、基因诊断结果、治疗过程进行分析,并进行相关文献复习.结果 患儿男,16个月,生后1月余开始反复发热、腹泻、咳喘、肝脾和淋巴结肿大、贫血（血红蛋白最低50g/L）、血小板减少（最低35×10^9/L）,多次查外周血白细胞计数正常,血清免疫球蛋白升高（IgG 19800 mg/L,IgA 1710 mg/L,IgM 2590 mg/L）,血清维生素B12＞ 1.5 pg/L,4次流式细胞术检测外周血CD3^＋ CD4^-CD8^-T细胞数明显增多（＞10％）,2次检测CD3^＋ TCRαβ^＋ CD4^-CD8^-T细胞数（DNTs）均＞3％,基因检测显示FAS基因编码区第309位杂合突变,诊断为ALPS.补充检查FAS诱导淋巴细胞凋亡功能实验阳性.给予泼尼松15 mg每日1次、霉酚酸酯125 mg每日3次治疗,血红蛋白和血小板维持正常水平,肝脾和淋巴结逐渐缩小,泼尼松逐渐减量,目前已接受治疗8个月,血红蛋白和血小板正常.在近10年国内外数据库中检索ALPS,国外报道400余例,国内仅有5例.5例中,4例自婴幼儿期发病.5例均有重度肝脾、淋巴结肿大伴随贫血（4例确诊为溶血性贫血）和血小板减少.3例有反复感染的病史,1例合并肾小球肾炎.5例血清免疫球蛋白＞正常上限1.5倍,3例血清维生素B12＞ 1.5 pg/L（余2例未测）,5例CD3^＋ CD4^-CD8^-T细胞均＞10％,2例DNTs细胞分别为8.9％和15.7％（余3例未测）.3例明确检测出FAS基因突变.5例均接受激素治疗,2例增加霉酚酸酯治疗,在初期1～3个月内治疗全部有效,缺乏长期随访报道.结论 自身免疫性淋巴增生综合征是T细胞凋亡异常所致的原发性免疫缺陷病,多数有FAS基因突变.婴幼儿期起病为主,临床以淋巴增生和自身免疫现象为突出表现,可伴随反复感染和过敏现象.血清维生素B12水平和CD3^＋ CD4^-CD8^-T细Objective To summarize the clinical characteristics,diagnosis and treatment of a case with autoimmune lymphoproliferative syndrome （ALPS）.Method The patient was diagnosed as autoimmune lymphoproliferactive syndrome （ALPS） after being admitted to the Department of Rheumatism and Immunology of Tianjin Children＇s Hospital in February 20,2014.The clinical characteristics,physical examination,laboratory tests,gene tests,and treatment process were analyzed and related literature was reviewed.Result The patient was a 16-month-old boy.Since the first month of life,he started to have repeatedly fever,diarrhea,shortness of breath,lymphadenopathy,hepatosplenomegaly,anemia（HGBmin 50 g/L） and thrombocytopenia （min 35 × 10^9/L）.But multiple exams showed a normal peripheral blood leukocyte count,hypergammaglobulinemia （IgG 19800 mg/L,IgA 1 710 mg/L,IgM 2 590 mg/L）and significantly increased serum vitamin B12.Flow cytometric measures showed that CD3 ^＋ CD4^-CD8^-T lymphocytes significantly increased （〉 10%） at four times.The count of CD3^ ＋ TCRαβ^＋ CD4^-CD8 T lymphocytes （double negative T cells; DNTs） 〉 3% twice.The genetic test showed that 309th FAS gene area showed heterozygous mutations,the boy was diagnosed as ALPS.Added examinations of lymphocytes apoptosis induced by FAS was positive.He was treated with prednisone 15 mg once daily and immunomodulator 150 mg three times a day,while in maintaining period with normal levels of hemoglobin and platelet,the dose of prednisone was reduced gradually.Till now,the patient has been treated and observed for 8 months.We retrieved the reports of ALPS in the databases at home and abroad published in recent 10 years,more than 400 cases reported from foreign countries,but there were only 5 domestic cases.Among those,4 had onset in infancy and 1 at 6-years of age.All the cases presented servere lymphadenopathy and hepatosplenomegaly with anemia （4 of them with hemolytic anemia） and thrombocytopenia.Three cases had a history of frequent infecti

关 键 词：原发性免疫缺陷病 自身免疫性淋巴增生综合征 儿童 诊断 治疗 

分 类 号：R725.9[医药卫生—儿科]