title: A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50.
abstract: 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=58-81pM). 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.
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA. Electronic address: serraelliott@engr.ucsb.edu.
authors.forename: Serra E
authors.initials: SE
authors.lastname: Elliott
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: nicholas.f.parchim@uth.tmc.edu.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Parchim
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: rodney.e.kellems@uth.tmc.edu.
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Kellems
authors.affiliation: Departments of Biochemistry and Molecular Biology, University of Texas Medical School at Houston, Houston, TX 77030, USA. Electronic address: yang.xia@uth.tmc.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Maternal-Fetal Medicine, Cottage Health System, Santa Barbara, CA 93105, USA. Electronic address: alex@greatbaby.com.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Soffici
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA 93106, USA. Electronic address: psd@engr.ucsb.edu.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Daugherty
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000276:immunology* / Q000378:metabolism; D010920:Placenta / Q000276:immunology* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; C509754:GPR50 protein, human; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C417029:EBV-encoded nuclear antigen 1
keywords: Antibody; Antigen discovery; Bacterial display; Epitope mapping; Peptide; Pre-eclampsia