Role of human leukocyte antigen alloantibodies and other immunological factors in pre-eclampsia

Background: The nature of rejection and fetal allograft survival following the host-versus-graft reactivity remains the subject of intense investigation. Pregnancy-induced hypertension, also known as pre-eclampsia, is a disease of the second half of pregnancies probably associated with some immunological factors. Aims and Objectives: This study aims to understand the key mechanisms of the immune process behind preeclampsia. Lymphocytes play a central role in orchestrating the cell-mediated immune response during pregnancy, ensuring maternal-fetal immune tolerance. Materials and Methods: The study involved 83 pre-eclamptic patients including 100 normal pregnancies. In the present investigation, pre-eclamptic patients were screened after proper clinical diagnosis and human leukocyte antigen (HLA) was typed using the standard two-stage micro lymphocytotoxicity test. HLA antibodies of the patients were screened against a well-known donor cell panel. Immunoglobulin (Ig) levels were measured using enzyme-linked immunosorbent assay and the immunoturbidity method. The status of CD3, CD4, and CD8 cells was found out using monoclonal antibodies resetting with dynabeads (Dynal, U.K.). Results: The incidence of alloantibodies (anti-HLA antibodies) against paternal antigens was observed more in the case of normal pregnancy when compared with patient group where the incidence was very low even rare in pre-eclampsia (28.08% vs. 3.07% in primiparous and 39.7% vs. 11.1% in multiparous women). The compatibility of HLA antigens between the couple of pre-eclamptic patients was found higher when compared with normal pregnancy (HLA-A 9.5 vs. 16.2% and HLA-DRB1 22.1 vs. 27.6%). The concentration of IgG was found lower and the concentration of IgM was found to be higher in pre-eclampsia than that of normal pregnancy. There is a slight increase in the ratio of CD4+ and CD8+ (1.09:1.67) or in other words, an increase in the number of CD4+ cells and decrease in CD8+ give a higher ratio in pre-eclampsia. Conclusion: The combination of increased HLA sharing and the absence of protective HLA alloantibodies in preeclampsia suggests a failure of normal maternal-fetal immune tolerance. This deficiency is associated with altered T cell function, especially a detrimental shift toward Th1 activity which is pro-inflammatory, and might contribute to the pathogenesis of preeclampsia.