Human serum antibodies against EBV latent membrane protein 1 cross-react with ?-synuclein.

ABSTRACT:

Objectives

To identify the epitope on ?-synuclein (?-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 ?-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 ?-syn (which differ from human ?-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 ?-syn and LMP1 containing the mimicry domain.

Results

CS1-4 showed strong reactivity to wild-type human ?-syn, but not to the mutant peptides or rodent ?-syn. Control EBV- and EBV+ sera showed no reactivity to ?-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 (? = 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 ?-syn peptides.

Conclusions

Anti-EBV-LMP1 antibodies cross-reacting with a defined epitope in ?-syn are present in human patients. These findings may have implications for the pathogenesis of synucleinopathies.

SUBMITTER: Woulfe J 

PROVIDER: S-EPMC4864620 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature