PMID- 36997584 OWN - NLM STAT- MEDLINE DCOM- 20230403 LR - 20230419 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Mar 30 TI - Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status. PG - 5232 LID - 10.1038/s41598-023-32156-9 [doi] LID - 5232 AB - 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 FcgammaRIIIA 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. CI - (c) 2023. The Author(s). FAU - Habets, Denise H J AU - Habets DHJ AD - Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl. AD - Department of Transplantation Immunology, Maastricht University Medical Centre, Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl. AD - GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. denise.habets@maastrichtuniversity.nl. FAU - Al-Nasiry, Salwan AU - Al-Nasiry S AD - Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands. AD - GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. FAU - Nagelkerke, Sietse Q AU - Nagelkerke SQ AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. AD - Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. FAU - Voorter, Christina E M AU - Voorter CEM AD - Department of Transplantation Immunology, Maastricht University Medical Centre, Maastricht, The Netherlands. AD - GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. FAU - Spaanderman, Marc E A AU - Spaanderman MEA AD - Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, The Netherlands. AD - GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. FAU - Kuijpers, Taco W AU - Kuijpers TW AD - Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. AD - Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. FAU - Wieten, Lotte AU - Wieten L AD - Department of Transplantation Immunology, Maastricht University Medical Centre, Maastricht, The Netherlands. AD - GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230330 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Receptors, IgG) RN - 0 (Antibodies) RN - 0 (HLA Antigens) RN - 0 (FCGR3A protein, human) SB - IM MH - Pregnancy MH - Humans MH - Female MH - *Receptors, IgG/metabolism MH - Killer Cells, Natural MH - Polymorphism, Single Nucleotide MH - Antibodies/metabolism MH - HLA Antigens/metabolism MH - *Abortion, Habitual PMC - PMC10063683 COIS- The authors declare no competing interests. EDAT- 2023/03/31 06:00 MHDA- 2023/04/03 06:42 PMCR- 2023/03/30 CRDT- 2023/03/30 23:18 PHST- 2022/08/02 00:00 [received] PHST- 2023/03/23 00:00 [accepted] PHST- 2023/04/03 06:42 [medline] PHST- 2023/03/30 23:18 [entrez] PHST- 2023/03/31 06:00 [pubmed] PHST- 2023/03/30 00:00 [pmc-release] AID - 10.1038/s41598-023-32156-9 [pii] AID - 32156 [pii] AID - 10.1038/s41598-023-32156-9 [doi] PST - epublish SO - Sci Rep. 2023 Mar 30;13(1):5232. doi: 10.1038/s41598-023-32156-9.