PDF(Pubmed)
Abstract：
Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene, located on chromosome 16 (16p13.3) and encoding the pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of the pathological processes leading to the spontaneous and recurrent autoinflammatory attacks observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool to study the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs from an Armenian patient with FMF carrying the M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. We found that the morphology of macrophages derived from iPSCs of a patient with the MEFV mutation significantly differed from that of macrophages derived from iPSCs of a healthy donor carrying the wild-type MEFV gene.
摘要：
家族性地中海热（FMF）是由MEFV（地中海FeVer）基因遗传突变引起的系统性自身炎症性疾病，位于染色体16（16p13.3），编码pyrin蛋白。尽管有关于MEFV突变的现有数据，它们对导致在FMF中观察到的自发性和复发性自身炎症发作的病理过程发展的确切机制，尚不清楚。诱导多能干细胞（iPSCs）由于其分化为任何细胞类型的能力，被认为是研究各种疾病的分子遗传机制的重要工具。包括巨噬细胞,这有助于FMF的发展。在这项研究中,我们开发了携带M694V的亚美尼亚FMF患者的iPSCs，p.（Met694Val）（c.208A>G，rs61752717）MEFV基因外显子10的致病性突变。由于直接分化，获得表达CD14和CD45表面标志物的巨噬细胞。我们发现来自具有MEFV突变的患者的iPSC的巨噬细胞的形态与来自携带野生型MEFV基因的健康供体的iPSC的巨噬细胞的形态显著不同。
