Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene
Hemophagocytic lymphohistiocytosis due to germline mutations in SH2D1A, the X-linked lymphoproliferative disease gene
复制标题
DOI：
10.1182/blood.v97.4.1131
复制
发表时间：
2001-02-15
期刊：
影响因子：
20.3
通讯作者：
Nichols, KE
中科院分区：
文献类型：
--
作者：
Arico, M;Imashuku, S;Nichols, KE
噬血细胞性淋巴组织细胞病（HLH）是一组以T细胞和巨噬细胞活化失调为特征的异质性疾病。尽管一些HLH患者携带穿孔素基因突变，但其余病例的原因尚不清楚。HLH的表型与X连锁淋巴组织增生性疾病（XLP）非常相似，XLP是一种EB病毒（EBV）相关的免疫缺陷，由SH2D1A缺陷引起，SH2D1A是一种在T淋巴细胞和自然杀伤细胞中表达的含SH2结构域的小蛋白。这里显示，25例接受检查的HLH男性患者中有4例携带生殖系SH2D1A突变。在这4例患者中，只有2例有与XLP一致的家族史。基于这些发现，建议所有患有EBV相关噬血细胞增多症的男性患者进行SH2D1A突变筛查，确定患有XLP的患者应接受遗传咨询，并长期随访淋巴瘤和低丙种球蛋白血症的发展。
The hemophagocytic lymphohistiocytoses (HLH) comprise a heterogeneous group of disorders characterized by dysregulated activation of T cells and macrophages, Although some patients with HLH harbor perforin gene mutations, the cause of the remaining cases is not known. The phenotype of HLH bears a strong resemblance to X-linked lymphoproliferative disease (XLP), an Epstein-Barr virus (EBV)- associated immunodeficiency resulting from defects in SH2D1A, a small SH2 domain-containing protein expressed in T lymphocytes and natural killer cells. Here it is shown that 4 of 25 male patients with HLH who were examined harbored germline SH2D1A mutations. Among these 4 patients, only 2 had family histories consistent with XLP. On the basis of these findings, it is suggested that all male patients with EBV-associated hemophagocytosis be screened for mutations in SH2D1A, Patients identified as having XLP should undergo genetic counseling, and be followed long-term for development of lymphoma and hypogammaglobulinemia.