Does differential HLA-E and -F expression cause an aberrant immune tolerance in preeclampsia and HELLP?

The non-classical HLA-groups (E, F, G), representing Minor Histocompatibility antigens (miHA) are essential for fetal-maternal immune tolerance and normal placental development. Reduced HLA-G expression on extravillous trophoblasts is linked to pregnancy disorders like preeclampsia (PE) due to weak trophoblast invasion in the maternal decidua.

We measured the RNA-expression level of HLA-F and -E in placental tissue by SYBRgreen based qPCR. We examined PE (n = 19), PE/SGA (n = 10), HELLP (n = 10), HELLP/SGA (n = 6), SGA (n = 18) and control (n = 25) tissues to determine a possible linkage of HLA-E and -F to placental disorders.

We detected a significant increase of HLA-E expression (p = 0.04) in PE vs. control (1.4-fold) placentas. Considering pregnancy outcome a significant increase was observed for HLA-F (p = 0.037) and -E (p = 0.037) for male infants in HELLP placentas (7.4-fold and 2.4-fold) with and without SGA and HLA-E (p = 0.033) in PE alone (2.1-fold) compared to the control cohort. However, no significant increase was observed within the female infant cohort for HLA-E and -F.

The significant upregulation of HLA-E in PE could indicate an upregulated antigen presentation resulting in an increased maternal immune response in PE. Concerning pregnancy outcome, the significant increased HLA-E in PE of male infants might additionally be enhanced by miHA. The further upregulated HLA-F in HELLP of male infants could mediate increased immune tolerance mechanisms, resulting in the symptoms of HELLP.