Worth Austen, Thrasher Adrian J, Gaspar H Bobby
Department of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UK.
Br J Haematol. 2006 Apr;133(2):124-40. doi: 10.1111/j.1365-2141.2006.05993.x.
Autoimmune lymphoproliferative syndrome (ALPS) is a variable clinical condition manifest by lymphoproliferative disease, autoimmune cytopenias and susceptibility to malignancy. Central to the cellular pathogenesis is defective FAS-induced apoptosis, which in turn leads to dysregulation of lymphocyte homeostasis. The majority of patients have heterozygous mutations in the FAS (TNFRSF6) gene, but the condition is genetically heterogeneous and mutations in FAS ligand and caspase-8 and caspase-10, all of which are involved in Fas mediated signalling, have also been identified. This review provides a detailed insight into the pathophysiology of lymphocyte apoptosis and how this relates to the variable and complex clinical manifestations of ALPS.
自身免疫性淋巴细胞增生综合征（ALPS）是一种临床表现多样的病症，其特征为淋巴增生性疾病、自身免疫性血细胞减少症以及易患恶性肿瘤。细胞发病机制的核心是FAS诱导的凋亡缺陷，这反过来又导致淋巴细胞稳态失调。大多数患者在FAS（TNFRSF6）基因中存在杂合突变，但该病症在遗传上具有异质性，并且还发现了FAS配体、半胱天冬酶-8和半胱天冬酶-10的突变，所有这些都参与Fas介导的信号传导。本综述详细阐述了淋巴细胞凋亡的病理生理学，以及这与ALPS多变且复杂的临床表现之间的关系。
