Associations of Epstein-Barr virus (EBV) and
autoimmune diseases have been hypothesized. We have analysed
IgG antibodies to
EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic
connective tissue diseases (CTD), exemplified by
systemic lupus erythematosus (SLE), primary
Sjogren's syndrome (SS),
rheumatoid arthritis (RA),
systemic sclerosis (SSc) and secondary SS (classical
CTDs complicated with SS). An
enzyme-linked
immunosorbent assay (ELISA) which uses
glutathione-S-transferase polypeptides fused to
EBV nuclear antigen (EBNA)-2 and
EBNA-1 was developed. Ratios of
IgG antibody reactivity to whole
IgG concentrations of sera were calculated to normalize EBNA-2 and
EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD(450) readings of
IgG antibodies to both the amino-terminal aa 1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of
EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to
EBNA-1. The OD readings were divided by serum
IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of
IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a
polyproline tract and a
proline-rich sequence and has considerable amino acid sequence homology with many cellular
proline-rich
proteins. High ratios of EBNA-2 aa 1-116 to
EBNA-1 aa 451-641
IgG antibody levels which probably suggest reactivation of EBV
latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and
proline-rich cellular
proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry-
epitope shift mechanism.