Abstract
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 HLA‑G 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 HLA‑G UTR4 in reducing the risk for allo-immunization.
Highlights
Alloreactive anti-human leukocyte antigen (HLA) antibodies formed during pregnancy are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion, such as febrile non-hemolytic transfusion reactions, immunological platelet refractoriness or transfusionrelated acute lung injury (TRALI) [1, 2].HLA Ib and Pregnancy Allo-ImmunizationSir Peter Medawar was among the first to recognize the immunological paradox of pregnancy
Much knowledge has been added to the field since pregnancy remains a model to study the development of allogenic tolerance and anti-HLA alloantibodies
Anti-HLA alloantibodies induced by pregnancy are of importance because of clinical adverse effects of pretransplantation donor-specific antibodies (DSA) in transfusion and in the graft
Summary
Alloreactive anti-human leukocyte antigen (HLA) antibodies formed during pregnancy are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion, such as febrile non-hemolytic transfusion reactions, immunological platelet refractoriness or transfusionrelated acute lung injury (TRALI) [1, 2].HLA Ib and Pregnancy Allo-ImmunizationSir Peter Medawar was among the first to recognize the immunological paradox of pregnancy. Alloreactive anti-human leukocyte antigen (HLA) antibodies formed during pregnancy are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion, such as febrile non-hemolytic transfusion reactions, immunological platelet refractoriness or transfusionrelated acute lung injury (TRALI) [1, 2]. The current study is in line with this important scientific theme by investigating a role of maternal HLA class Ib polymorphisms in pregnancy allo-immunization. Studies on pregnancy-induced alloimmunization have shown that 18 to 74% of women with a history of pregnancy have antiHLA alloantibodies. The level of antiHLA antibodies increases with the number of pregnancies and the number of children delivered [1,2,3,4,5]. Biological and genetic factors have been associated with pregnancy-induced anti-HLA alloimmunization, the process remains poorly understood
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