Scientific Reports ( IF 3.8 ) Pub Date : 2023-03-30 , DOI: 10.1038/s41598-023-32156-9 Denise H J Habets 1, 2, 3 , Salwan Al-Nasiry 1, 3 , Sietse Q Nagelkerke 4, 5 , Christina E M Voorter 2, 3 , Marc E A Spaanderman 1, 3 , Taco W Kuijpers 4, 5 , Lotte Wieten 2, 3
Natural Killer (NK) cells have been implicated in recurrent pregnancy loss (RPL). The p.Val176Phe (or Val158Phe) Single Nucleotide Polymorphism (SNP) in the FCGR3A gene encoding the FcγRIIIA or CD16a receptor has been associated with an enhanced affinity for IgG and stronger NK-mediated antibody-dependent cellular cytotoxicity. We hypothesized that the presence of at least one p.176Val variant associates with RPL and increased CD16a expression and alloantibodies e.g., against paternal human leukocyte antigen (HLA). In 50 women with RPL, we studied frequencies of the p.Val176Phe FCGR3A polymorphisms. Additionally, CD16a expression and anti-HLA antibody status were analyzed by flowcytometry and Luminex Single Antigens. In woman with RPL, frequencies were: 20% (VV), 42% (VF) and 38% (FF). This was comparable to frequencies from the European population in the NCBI SNP database and in an independent Dutch cohort of healthy women. NK cells from RPL women with a VV (22,575 [18731-24607]) and VF (24,294 [20157-26637]) polymorphism showed a higher expression of the CD16a receptor than NK cells from RPL women with FF (17,367 [13257-19730]). No difference in frequencies of the FCGR3A-p.176 SNP were detected when comparing women with or without class I and class II anti-HLA antibodies. Our study does not provide strong evidence for an association between the p.Val176Phe FCGR3A SNP and RPL.
中文翻译:
复发性流产女性 FCGR3A-p.176Val 变异分析及其与 CD16a 表达和抗 HLA 抗体状态的关联
自然杀伤 (NK) 细胞与复发性流产 (RPL) 有关。编码 FcγRIIIA 或 CD16a 受体的FCGR3A基因中的 p.Val176Phe(或 Val158Phe)单核苷酸多态性 (SNP)与增强的 IgG 亲和力和更强的 NK 介导的抗体依赖性细胞毒性有关。我们假设至少一种 p.176Val 变体的存在与 RPL 和增加的 CD16a 表达和同种抗体有关,例如,针对父本人类白细胞抗原 (HLA)。在 50 名患有 RPL 的女性中,我们研究了 p.Val176Phe FCGR3A的频率多态性。此外,通过流式细胞术和 Luminex 单一抗原分析 CD16a 表达和抗 HLA 抗体状态。在患有 RPL 的女性中,频率为:20% (VV)、42% (VF) 和 38% (FF)。这与 NCBI SNP 数据库中欧洲人群和荷兰独立健康女性队列中的频率相当。来自具有 VV (22,575 [18731-24607]) 和 VF (24,294 [20157-26637]) 多态性的 RPL 女性的 NK 细胞显示 CD16a 受体的表达高于来自具有 FF (17,367 [13257-19730]) 的 RPL 女性的 NK 细胞). 比较具有或不具有 I 类和 II 类抗 HLA 抗体的女性时,未检测到FCGR3A -p.176 SNP的频率差异。我们的研究没有提供强有力的证据证明 p.Val176Phe FCGR3A之间的关联SNP 和 RPL。