Fetal HLA-G alleles and their effect on miscarriage.

BACKGROUND Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels. OBJECTIVES The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date. MATERIAL AND METHODS The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing. RESULTS For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation. CONCLUSIONS HLA-G alleles seem to be related with miscarriage and should be considered in RM cases.

[1]  Leonardo Ferreira HLA-G and immune tolerance in pregnancy , 2018 .

[2]  M. Sanati,et al.  HLA-G allele and haplotype frequencies in a healthy population of Iran. , 2014, Iranian journal of allergy, asthma, and immunology.

[3]  R. Nanan,et al.  Innate and Adaptive Immune Interactions at the Fetal–Maternal Interface in Healthy Human Pregnancy and Pre-Eclampsia , 2014, Front. Immunol..

[4]  T. Hviid,et al.  The Many Faces of Human Leukocyte Antigen-G: Relevance to the Fate of Pregnancy , 2014, Journal of immunology research.

[5]  W. Yeung,et al.  Soluble Human Leukocyte Antigen-G5 Activates Extracellular Signal-Regulated Protein Kinase Signaling and Stimulates Trophoblast Invasion , 2013, PloS one.

[6]  B. Baradaran,et al.  HLA-G Expression Pattern: Reliable Assessment for Pregnancy Outcome Prediction. , 2013, Advanced pharmaceutical bulletin.

[7]  Jian Zhang,et al.  β2-Microglobulin-free HLA-G activates natural killer cells by increasing cytotoxicity and proinflammatory cytokine production. , 2013, Human immunology.

[8]  C. Ober,et al.  HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq. , 2012, Human immunology.

[9]  Mette Nielsen,et al.  Human leukocyte antigen-G in the male reproductive system and in seminal plasma. , 2011, Molecular human reproduction.

[10]  E. Carosella,et al.  Tolerogenic Function of Dimeric Forms of HLA-G Recombinant Proteins: A Comparative Study In Vivo , 2011, PloS one.

[11]  J. S. Hunt,et al.  Synthesis of β2‐microglobulin‐free, disulphide‐linked HLA‐G5 homodimers in human placental villous cytotrophoblast cells , 2007, Immunology.

[12]  R. Apps,et al.  A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1 , 2007, European journal of immunology.

[13]  K. Maenaka,et al.  Immune modulation of HLA-G dimer in maternal-fetal interface , 2007, European journal of immunology.

[14]  J. McCluskey,et al.  Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Wei-Hua Yan,et al.  Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition. , 2005, Cell research.

[16]  C. Ober,et al.  Variation in the HLA-G promoter region influences miscarriage rates. , 2003, American journal of human genetics.

[17]  Jacques Cohen,et al.  Genotyping: the HLA system and embryo development. , 2002, Reproductive biomedicine online.