A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50

- We present a method to discern environmental and human antibody targets in disease.
- An epitope-specific antibody response to EBNA-1 is associated with pre-eclampsia.
- This IgG1 anti-EBNA-1 antibody cross-reacts with human placental protein GPR50.

To characterize antibody specificities associated with pre-eclampsia (PE), bacterial displayed peptide library screening and evolution was applied to identify peptide epitopes recognized by plasma antibodies present in women with PE near the time of delivery. Pre-eclamptic women exhibited elevated IgG1 titers towards a peptide epitope KRPSCIGCK within the Epstein-Barr virus nuclear antigen 1 (EBNA-1). EBNA-1 epitope antibodies cross-reacted with a similar epitope within the extracellular N-terminus of the human G protein-coupled receptor, GPR50, expressed in human placental tissue and immortalized placental trophoblast cells. We observed increased antibody binding activity to epitopes from EBNA-1 and GPR50 among women with PE (n = 42) compared to healthy-outcome pregnancies (n = 43) and nulligravid samples (n = 21). The EBNA-1 peptide potently blocked binding of the PE-associated antibody to the GPR50 epitope (IC50 = 58-81 pM). These results reveal the existence of molecular mimicry between EBNA-1 and placental GPR50, supporting a mechanism for IgG1 deposition in the pre-eclamptic placenta.