title: 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.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Laboratory of Immunogenetics and Histocompatibility (LIGH), Genetics Department, Federal University of Paraná, Curitiba, Brazil.|Capes Foundation, Ministry of Education of Brazil, Brasília, Brazil.
authors.forename: Fabiola da Silva
authors.initials: Fda S
authors.lastname: Nardi
authors.affiliation: Laboratory of Immunogenetics and Histocompatibility (LIGH), Genetics Department, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Slowik
authors.affiliation: Reproductive Immunology Center, Porto Alegre, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Michelon
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Capes Foundation, Ministry of Education of Brazil, Brasília, Brazil.
authors.forename: Luis Felipe Dos Santos
authors.initials: LF
authors.lastname: Manvailer
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Reproductive Immunology Center, Porto Alegre, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Horn
authors.affiliation: Laboratory of Immunogenetics and Histocompatibility (LIGH), Genetics Department, Federal University of Paraná, Curitiba, Brazil.
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Bicalho
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Rebmann
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000067128:Extracellular Vesicles / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000628:therapy; D011110:Polymorphism, Genetic; D011247:Pregnancy; D017384:Sequence Deletion / Q000235:genetics*; D017211:Treatment Failure
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: 14-bp ins/del polymorphism; extracellular vesicles; human leukocyte antigen-G; implantation failure; soluble HLA-G; vesicular sHLA-G