Drappa J, Vaishnaw A K, Sullivan K E, Chu J L, Elkon K B
Division of Rheumatology, Hospital for Special Surgery, Cornell University Medical Center, New York, NY 10021, USA.
N Engl J Med. 1996 Nov 28;335(22):1643-9. doi: 10.1056/NEJM199611283352204.
The Canale-Smith syndrome is a childhood disorder characterized by lymphadenopathy and autoimmunity. The similarity between this syndrome and that in mice with the lymphoproliferation (lpr) phenotype or the generalized-lymphoproliferative-disease (gld) phenotype led us to investigate whether it too is caused by mutations of the Fas gene (lpr mice) or the Fas ligand (gld mice), which regulate apoptosis in lymphocytes.
We studied four patients with the syndrome and their families. T-lymphocyte phenotypes were analyzed, and the susceptibility of activated T cells to Fas-mediated apoptosis in vitro was determined. Mutations of Fas were sought by nucleotide-sequence analysis.
Patients with the Canale-Smith syndrome had increased numbers of circulating double-negative T cells (>20 percent) and profoundly impaired apoptosis of activated T cells incubated with an anti-Fas antibody. Three novel Fas mutations were identified, all of which were heterozygous and predicted to impair signal transduction by Fas. Autoimmune manifestations of the disease, such as hemolytic anemia and thrombocytopenia, persisted into adolescence. Two patients followed into adulthood had intermittent lymphadenopathy, which diminished over time. Neoplasms developed in both, and one died of hepatocellular carcinoma at the age of 43.
Patients with the Canale-Smith syndrome have mutations in Fas, which implicates this gene in the accumulation of lymphocytes and the autoimmunity characteristic of the syndrome.
卡纳莱 - 史密斯综合征是一种儿童期疾病，其特征为淋巴结病和自身免疫。该综合征与具有淋巴细胞增殖（lpr）表型或全身性淋巴细胞增殖性疾病（gld）表型的小鼠疾病相似，这促使我们研究它是否也由调节淋巴细胞凋亡的Fas基因（lpr小鼠）或Fas配体（gld小鼠）突变引起。
我们研究了4例患有该综合征的患者及其家族。分析了T淋巴细胞表型，并测定了活化T细胞在体外对Fas介导的凋亡的敏感性。通过核苷酸序列分析寻找Fas突变。
卡纳莱 - 史密斯综合征患者循环双阴性T细胞数量增加（>20%），且与抗Fas抗体孵育的活化T细胞凋亡严重受损。鉴定出3种新的Fas突变，均为杂合子，预计会损害Fas的信号转导。该疾病的自身免疫表现，如溶血性贫血和血小板减少症，持续至青春期。随访至成年期的2例患者有间歇性淋巴结病，随时间推移而减轻。两人均发生肿瘤，其中一人43岁时死于肝细胞癌。
卡纳莱 - 史密斯综合征患者存在Fas突变，这表明该基因与淋巴细胞积聚及该综合征的自身免疫特征有关。
