INSERM UMR 1163, Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Paris F-75015, France; Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris F-75015, France.
Curr Opin Immunol. 2017 Dec;49:79-86. doi: 10.1016/j.coi.2017.10.001. Epub 2017 Oct 23.
The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. This clinical entity was recognized in the mid 60s and its genetic etiology was described in 1995 by the discovery of the FAS gene mutations. This was the first description of a monogenic cause of autoimmunity but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic causes of ALPS such as somatic mutations of RAS or the recently described CTLA-4 insufficiency. The recognition of these genetic diseases brought new information on the regulation of the adaptive immune responses and uncovered new therapeutical targets. Finally, the deciphering the role of somatic mutations may pave the way to the understanding of more common autoimmune diseases.
自身免疫性淋巴增生综合征（ALPS）是一种非恶性、非传染性的淋巴细胞失控性增殖，伴有自身免疫性血细胞减少症。这一临床实体在 60 年代中期被认识到，其遗传病因在 1995 年通过 Fas 基因突变的发现被描述。这是自身免疫性疾病的第一个单基因病因描述，但直到在 ALPS 患者中描述了体细胞和种系突变，其非孟德尔式表达仍难以捉摸。相关的凋亡缺陷导致自身反应性淋巴细胞的积累，以及区分 ALPS-FAS 与其他单基因病因（如 RAS 的体细胞突变或最近描述的 CTLA-4 不足）的特定临床和生物学特征。这些遗传疾病的认识带来了关于适应性免疫反应调节的新信息，并揭示了新的治疗靶点。最后，对体细胞突变作用的解读可能为理解更常见的自身免疫性疾病铺平道路。
