X-Linked Lymphoproliferative Disease Type 1: A Clinical and Molecular Perspective.
X-Linked Lymphoproliferative Disease Type 1: A Clinical and Molecular Perspective.
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DOI：
10.3389/fimmu.2018.00666
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发表时间：
2018
影响因子：
7.3
通讯作者：
Schwartzberg PL
中科院分区：
文献类型：
--
作者：
Panchal N;Booth C;Cannons JL;Schwartzberg PL
X连锁淋巴组织增生性疾病（XLP）最早于20世纪70年代被描述为与EB病毒（EBV）感染相关的致命性淋巴组织增生综合征。特征包括噬血细胞性淋巴组织细胞增生症（HLH）、淋巴瘤和异常丙种球蛋白血症。致病基因SH2D1A的分子克隆提供了对疾病性质的深入了解，并有助于表征正常免疫细胞功能的多种特征。虽然XLP 1型（XLP1）提供了一个原发性免疫缺陷的例子，其中患者主要有一个感染因子清除的问题，很明显，XLP1也是一种严重的免疫失调的疾病，甚至独立于EBV感染。在这里，我们描述了XLP1的临床特征，以及基因产物SAP和相关信号淋巴细胞活化分子家族受体的分子和生物学研究如何为疾病发病机制（包括特定免疫细胞缺陷）和当前治疗方法（包括潜在用途）提供见解基因疗法。这些研究共同帮助改变了这种曾经几乎一致致命的疾病的结果。
X-linked lymphoproliferative disease (XLP) was first described in the 1970s as a fatal lymphoproliferative syndrome associated with infection with Epstein–Barr virus (EBV). Features include hemophagocytic lymphohistiocytosis (HLH), lymphomas, and dysgammaglobulinemias. Molecular cloning of the causative gene, SH2D1A, has provided insight into the nature of disease, as well as helped characterize multiple features of normal immune cell function. Although XLP type 1 (XLP1) provides an example of a primary immunodeficiency in which patients have problems clearing primarily one infectious agent, it is clear that XLP1 is also a disease of severe immune dysregulation, even independent of EBV infection. Here, we describe clinical features of XLP1, how molecular and biological studies of the gene product, SAP, and the associated signaling lymphocyte activation molecule family receptors have provided insight into disease pathogenesis including specific immune cell defects, and current therapeutic approaches including the potential use of gene therapy. Together, these studies have helped change the outcome of this once almost uniformly fatal disease.