Service de Médecine Interne et Vasculaire B, CHRU de Tours, France, Tours, France.
Rheumatol Int. 2012 Jul;32(7):2203-7. doi: 10.1007/s00296-011-2026-4. Epub 2011 Jul 23.
Hypothesizing a pathophysiological role of anti-topoisomerase I antibodies (anti-topo I) through autoantibody-dependent cell-mediated cytotoxicity (ADCC) and cytotoxic effectors expressing receptors for the Fc portion of IgG in systemic sclerosis (SSc), 267 SSc patients (56 with anti-topo I and 102 with anti-centromere antibodies (ACA)) were genotyped for the functional FCGR3A-V158F polymorphism. A descriptive analysis of patients according to their clinical and immunological status and FCGR3A-158 V/F genotypes was performed using multiple correspondence analysis. This descriptive analysis revealed an association between the FCGR3A-158 VV genotype and the presence of anti-topo I. By contrast, no relationship was found between FCGR3A polymorphism and the presence of ACA. SSc patients with anti-topo I appear to be more frequently homozygous for the high-affinity FcγRIIIA-coding allele, suggesting that some autoantibodies may be pathogenic through ADCC.
通过抗拓扑异构酶 I 抗体（抗拓扑 I）的自身抗体依赖性细胞介导的细胞毒性（ADCC）和表达 IgG Fc 部分受体的细胞毒性效应物，假设其在系统性硬化症（SSc）中的病理生理作用，对 267 名 SSc 患者（56 名抗拓扑 I 阳性和 102 名抗着丝点抗体阳性）进行了功能 FCGR3A-V158F 多态性的基因分型。使用多元对应分析对根据其临床和免疫学状态以及 FCGR3A-158 V/F 基因型的患者进行描述性分析。该描述性分析显示 FCGR3A-158 VV 基因型与抗拓扑 I 的存在之间存在关联。相比之下，FCGR3A 多态性与 ACA 的存在之间没有关系。抗拓扑 I 的 SSc 患者似乎更常为高亲和力 FcγRIIIA 编码等位基因的纯合子，表明一些自身抗体可能通过 ADCC 具有致病性。
