自身免疫性淋巴细胞增生综合征1例并文献复习

Autoimmune lymphoproliferative syndrome: a case report and literature review

报道2013年10月北京大学第一医院诊治的1例自身免疫性淋巴细胞增生综合征(autoimmune lymphoproliferative syndrome,ALPS)的临床诊疗过程,并复习国内外最新文献。该男性患儿就诊时为11个月,生后早期起病,病程中主要表现为淋巴结、肝脾肿大,伴溶血性贫血、慢性感染(巨细胞病毒、细小病毒B19感染以及慢性腹泻),外周血双阴性T细胞(double negative T cells,DNTs)明显升高(占淋巴细胞的27.18%,CD3+T淋巴细胞的35.16%),多种自身抗体阳性(包括抗核抗体、双链DNA、类风湿因子)以及高丙种球蛋白血症。父母双方均体健,否认自身免疫性疾病病史。经基因诊断提示存在FAS基因c.309A>C杂合突变,位于FAS基因3号外显子,导致FAS蛋白第103位氨基酸由精氨酸(R)突变为丝氨酸(S)。但基因结果仍需进一步验证父母双方基因及正常对照,明确是否为致病基因。该患儿临床经过糖皮质激素治疗,并在外院接受霉酚酸酯治疗,贫血改善,仍有反复感染,肝脾回缩但未至正常。ALPS的特征是编码细胞Fas/Fas L凋亡途径的基因发生突变引起的一组临床症候群,特点突出,早期容易误诊为其他疾病,需对外周血淋巴细胞进行分析,治疗手段主要依赖于免疫抑制剂治疗。

We described 1 case of autoimmune lymphoproliferative syndrome（ ALPS）,first diagnosed in our hospital,and reviewed the recent literature. The 11-month old male patient presented with a history of splenomegaly and hepatomegaly since 1 month after birth. He suffered recurrent infectious diseases including cytomegalovirus infection,parvovirus B19 infection and chronic diarrhea disease. Besides,his symptoms included hemolytic anemia and thrombocytopenia. The laboratory abnormality indicated an expanded population of alpha / beta double-negative T cells（ DNTs）（ 27. 18% of lymphocytes,35. 16% of CD3＋T lymphocytes） in peripheral blood,and autoantibodies including antinuclear antibody,doublestranded DNA and rheumatic factor were positive. Hyper gamma globulinemia and positive direct Coombs tests were seen in the patient. His parents were both healthy and denied autoimmune diseases. We identified a heterozygous point mutation in exon 3 of the FAS gene carrying c. 309 A C,resulting in a single base pair substitution in exon 3 of FAS gene which changed the codon of Arg103 to Ser103. Unfortunately,we were unable to obtain the gene results of the child＇s parents. The patient was treated with glucocorticoids in our hospital and with mycophenolatemofetil in other hospital. And we were informed that his anemia condition relieved through the telephone follow-up,but he still suffered recurrent infections,hepatomegaly and splenomegaly still existed. As we all know ALPS is characterized by defective lymphocyte apoptosis,and thus cause lymphoproliferative disease and autoimmune disease,and increase the risk of lymphoma. It is more likely to be misdiagnosed as other diseases. ALPS should be suspected in the case of chronic lymphadenopathy,splenomegaly and autoimmune features. Flow cytometry approach is helpful for the diagnosis. Immunosuppressive drugs are the necessary treatment.