1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
1] Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy [2] Department of Health Sciences, University of Piemonte Orientale 'Amedeo Avogadro', Novara, Italy.
Genes Immun. 2015 Jan-Feb;16(1):99-102. doi: 10.1038/gene.2014.59. Epub 2014 Oct 30.
Perforin (PRF) has a key role in the function of cytotoxic T and natural killer cells. Rare variations of PRF1 predispose to autoimmunity. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, involving defective lymphocyte apoptosis. The aim of this study was to investigate the role of PRF1 in CIDP. The entire coding region of PRF1 was sequenced in 94 patients and 158 controls. We found three missense variations leading to amino acid substitutions and one nonsense variation resulting in a premature stop codon. All variations would decrease PRF activity. Their overall frequency was significantly higher in patients than in controls (odds ratio (OR)=4.47). The most frequent variation was p.Ala91Val (OR=3.92) previously associated with other autoimmune diseases. Clinical analysis showed that PRF1 variations were more frequent in relapsing patients and in patients displaying axonal damage. These data suggest that PRF1 variations may influence CIDP development and course.
穿孔素 (PRF) 在细胞毒性 T 细胞和自然杀伤细胞的功能中起关键作用。PRF1 的罕见变异易导致自身免疫。慢性炎症性脱髓鞘性多发性神经病 (CIDP) 是一种影响周围神经系统的自身免疫性疾病，涉及淋巴细胞凋亡缺陷。本研究旨在探讨 PRF1 在 CIDP 中的作用。对 94 例患者和 158 例对照者的 PRF1 全长编码区进行测序。我们发现了三个导致氨基酸替换的错义变异和一个导致提前终止密码子的无义变异。所有的变异都会降低 PRF 的活性。与对照组相比，这些变异在患者中的总体频率显著更高（比值比 (OR)=4.47）。最常见的变异是 p.Ala91Val（OR=3.92），先前与其他自身免疫性疾病有关。临床分析表明，PRF1 变异在复发患者和存在轴索损伤的患者中更为常见。这些数据表明 PRF1 变异可能影响 CIDP 的发生和病程。
