High Amounts of Total and Extracellular Vesicle-Derived Soluble HLA-G are Associated with HLA-G 14-bp Deletion Variant in Women with Embryo Implantation Failure.

Abstract

Human leukocyte antigen-G (HLA-G) expression is related to 14-bp insertion/deletion polymorphism at the 3'UTR of the HLA-G gene. Soluble forms of HLA-G are released as free molecules or via extracellular vesicles (EVs). Due to the crucial role of HLA-G during pregnancy, we analyzed the 14-bp polymorphism and the two secreted forms in implantation failure women (IF) and in fertile women (FW). For the genetic analysis, 49 IF and 34 FW were genotyped. For sHLA-G quantification, serum samples from 35 IF and 23 FW were available. ExoQuick(™) kit was used for EVs precipitation. The total soluble HLA-G (sHLA-Gtot ) and vesicular sHLA-GEV were quantified by ELISA. The EVs size and concentration were determined by nanoparticle tracking analysis (NTA). An increased proportion of IF presented high levels of sHLA-Gtot (P = 0.02) and vesicular sHLA-GEV (P = 0.0003) compared to FW. The 14-bp deletion allele is more frequent in IF (P = 0.0002) and associated with high levels of sHLA-Gtot and vesicular sHLA-GEV . The high expression of sHLA-Gtot and sHLA-GEV , together with the presence of the 14-bp deletion allele, might be involved in implantation failure.