Antibody-Dependent Cytotoxicity of Monocytes in Preeclampsia Is Associated with Soluble Forms of HLA

Preeclampsia (PE) is a serious gestational complication that affects the lives of the mother and the child. Women with PE showed higher levels of pro-inflammatory cytokines secreted by leukocytes compared with women with normal pregnancies. The differences are most noticeable in the percentage of CD16+ monocytes, although the mechanism underlying this increase remains unclear. The CD16 receptor is critical for antibody-dependent cellular cytotoxicity, and by binding to antibodies on the surface of target cells, it activates their death. In this study, we examined the effect of soluble placental factors on the expression of CD16 monocytes and the potential role the soluble form of human leukocyte antigen (HLA) has on CD16 monocyte expression. At the first stage of our study, we collected samples of placental villi fragments from 58 pregnant women (38 women with PE and 20 with a healthy pregnancy). Then we studied the effect of placental villus-conditioned culture medium on CD16 expression by monocytes derived from the same women. It was shown that the content of CD16+ monocytes increased significantly in women with PE within 3 h and to a lesser extent in women with a healthy pregnancy (<i>p</i> = 0.009). Also, the addition of the recombinant histocompatibility HLA-B to the placental villus-conditioned culture medium blocks the induction of CD16 expression on monocytes. At the second stage of our study, we typed HLA class I and class II alleles in the umbilical cord blood samples and the venous blood samples taken from 38 women with PE and 40 women with a normal pregnancy. It was found that certain HLA class II alleles predominate in women with preeclampsia. The DRB1*01:01:01G allele showed the greatest difference (<i>p</i> < 0.001). Analyzing five alleles simultaneously makes it possible to predict the PE with AUC = 0.76. Evaluation of unique children's alleles also showed that class II alleles have greater differences among them than class I alleles. The DQB1*06:03:01G allele had the greatest differences with <i>p</i> = 0.03 (the number was higher in the control group). Performing an analysis of four alleles of children simultaneously allowed us to predict PE with an AUC of 0.64. This work suggests that the activation of CD16+ monocyte expression occurs due to the interaction of soluble placental antigens with monocytes. The most likely way to activate CD16 expression on monocytes is by HLA class II (both maternal and fetal) interaction with CD4 receptors on the surface of monocytes, whereas HLA class I is capable of blocking this process. Evaluation of maternal HLA alleles may be a significant marker for predicting PE.