title: Human serum antibodies against EBV latent membrane protein 1 cross-react with α-synuclein.
abstract: OBJECTIVE
  To identify the epitope on α-synuclein (α-syn) to which antibodies against the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera.
  
  
  METHODS
  Reactivity of the α-syn-cross-reacting anti-LMP1 monoclonal antibody CS1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat α-syn (which differ from human α-syn at this site) in Western blots. Using ELISA, sera from EBV+ (n = 4) and EBV- (n = 12) donors as well as those with infectious mononucleosis (IM; n = 120), and Hodgkin disease (HD; n = 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of α-syn and LMP1 containing the mimicry domain.
  
  
  RESULTS
  CS1-4 showed strong reactivity to wild-type human α-syn, but not to the mutant peptides or rodent α-syn. Control EBV- and EBV+ sera showed no reactivity to α-syn or LMP1 peptides. However, a significant proportion of IM and HD sera contained immunoglobulin M (IgM) (59% and 70%, in IM and HD, respectively), immunoglobulin G (IgG) (40% and 48%), and immunoglobulin A (IgA) (28% and 36%) antibodies to both peptides, as well as a significant correlation in the titers of IgM (ρ = 0.606 and 0.664, for IM and HD, respectively), IgG (0.526 and 0.836), and IgA (0.569 and 0.728) antibodies targeting LMP1 and α-syn peptides.
  
  
  CONCLUSIONS
  Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in α-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies.
authors.affiliation: Ottawa Hospital Research Institute and University of Ottawa (J.W.); University of Calgary (M.T.G.), Canada; and the Department of Pathology (M.S.G., J.M.M.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: Woulfe
authors.affiliation: Ottawa Hospital Research Institute and University of Ottawa (J.W.); University of Calgary (M.T.G.), Canada; and the Department of Pathology (M.S.G., J.M.M.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Madison T
authors.initials: MT
authors.lastname: Gray
authors.affiliation: Ottawa Hospital Research Institute and University of Ottawa (J.W.); University of Calgary (M.T.G.), Canada; and the Department of Pathology (M.S.G., J.M.M.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Munisha S
authors.initials: MS
authors.lastname: Ganesh
authors.affiliation: Ottawa Hospital Research Institute and University of Ottawa (J.W.); University of Calgary (M.T.G.), Canada; and the Department of Pathology (M.S.G., J.M.M.), VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Middeldorp