Maternal HLA Ib Polymorphisms in Pregnancy Allo-Immunization.

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib (HLA-E, -F and -G). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs. 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA­G and HLA-F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA­G UTR4 in reducing the risk for allo-immunization.

Cytokine stimulation of the choriocarcinoma cell line JEG-3 leads to alterations in the HLA-G expression profile.

The checkpoint molecule human leukocyte antigen (HLA)-G has restricted tissue expression, and plays a role in the establishment of maternal tolerance to the semi-allogenic fetus during pregnancy by expression on the trophoblast cells in the placenta. HLA-G exists in at least seven well-described mRNA isoforms, of which four are membrane-bound and three soluble. Regulation of the tissue expression of HLA-G and its isoforms is relatively unknown. Therefore, it is important to understand the regulation of HLA-G, and the HLA-G+ choriocarcinoma cell line JEG-3 is a widely used cellular model. We hypothesized that cytokines present in the microenvironment can regulate the HLA-G expression profile. In the present study, we systematically stimulated JEG-3 cells with various concentrations of IL-2, IL-4 IL-6, IL-10, IL-12, IL-15, IL-17A, TGF-ß1, TNF-α and IFN-γ1b. The results suggest that IFN-γ plays a role in maintenance of HLA-G expression, while IL-10 might be involved in regulation of the isoform profile.