In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with
rheumatoid arthritis (RA) and to compare it with the two major
autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with
systemic lupus erythematosus (SLE), and 28 healthy controls (HCs) were investigated by
enzyme-linked
immunosorbent assays (ELISA). Increased percentages of positives and concentrations of
IgG/
IgA/
IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1) were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of
IgG/
IgA/
IgM against the early lytic EBV
antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated
EBNA-1 IgA and
EBNA-1 IgM levels and the presence of
IgM and
IgA rheumatoid factors (RFs) and
anti-citrullinated protein antibodies (
ACPAs,
IgG) and between elevated
IgA concentrations against EAD and the presence of RFs and
ACPAs in RA patients were found. Thus, RA patients had elevated
antibodies of all isotypes characteristic of latent
EBV infection (whereas SLE patients had elevated
antibodies characteristic of lytic
EBV infection). Notably, for
IgM and
IgA (but not
IgG), these were associated with the presence of characteristic RA
autoantibodies.