Department of Immunology, La Paz University Hospital, Madrid, Spain.
Department of Immunology, La Paz University Hospital, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER U767), Madrid, Spain; La Paz Institute of Biomedical Research, Madrid, Spain.
Clin Immunol. 2021 Sep;230:108812. doi: 10.1016/j.clim.2021.108812. Epub 2021 Jul 27.
Autoimmune lymphoproliferative syndrome is a primary immunodeficiency caused by variants in FAS-mediated apoptosis related genes and is characterized by lymphadenopathy, splenomegaly and autoimmunity. A total of six different variants in CASP10 have been described as potential causative of disease, although two of them have recently been considered polymorphisms. The high allele frequency of these variants in healthy population in addition to the broad clinical spectrum of the disease difficult the interpretation of their pathogenicity. Here, we describe the clinical and analytical findings of three new patients carrying variants in CASP10 and summarize 12 more cases from the literature. Autoimmune cytopenias, adenopathies and increment of TCRαβ+CD4-CD8- cells have been the most common findings, being possibly the FAS-mediated apoptosis pathway the pathogenic mechanism of this disease. The clinical impact and the consequences of CASP10 variants are not fully elucidated, therefore the description of new cases will contribute to solve this issue.
自身免疫性淋巴增生综合征是一种由 Fas 介导的细胞凋亡相关基因变异引起的原发性免疫缺陷病，其特征为淋巴结病、脾肿大和自身免疫。目前已经描述了 CASP10 中的 6 种不同的变异体可能是疾病的潜在原因，尽管其中两种最近被认为是多态性。这些变异体在健康人群中的高等位基因频率，加上疾病的广泛临床谱，使得它们的致病性难以解释。在这里，我们描述了携带 CASP10 变异体的 3 名新患者的临床和分析结果，并总结了文献中的 12 例。自身免疫性血细胞减少症、淋巴结病和 TCRαβ+CD4-CD8-细胞的增加是最常见的发现，Fas 介导的细胞凋亡途径可能是该疾病的发病机制。CASP10 变异体的临床影响和后果尚未完全阐明，因此描述新病例将有助于解决这个问题。
