Elevated antinuclear antibodies and altered anti-Epstein-Barr virus immune responses

• High EBV VCA and EA IgG levels are present in ANA and ENA positive patients.
• High EBV VCA IgM were more frequent in patients with very high ANA titers.
• Anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in patients.
• Acute EBV infection/reactivation involved in the ANA/ENA autoantibody formation.

It has been shown that Epstein-Barr virus (EBV) is able to alter the immune response towards self-antigens and may enhance risk of autoimmune diseases such as systemic lupus erythematosus (SLE) in genetically predisposed individuals. In this study, we evaluated the specific antibody immune response against EBV in patients with anti-nuclear autoantibodies (ANA) in comparison with ANA-negative healthy controls. For this purpose, 92 patients with an high anti-ANA reactivity with or without concomitant extractable nuclear antigen (ENA) or double stranded DNA (dsDNA) positivity were selected and compared with 146 healthy donors. We found that anti-EBV-VCA and EA IgG concentrations were significantly higher in ANA-positive patients in comparison to the controls (VCA P < 0.0001 and EA P < 0,03) as well as in those ANA-positive patients that showed a concomitant ENA positivity (P = 0.0002). Interestingly, elevated anti-EBNA-1 IgG was found in a group of patients who had anti SSA/Ro antibodies. Anti-VCA IgM Abs were more frequently found in those patients with a very high titer of ANA (P = 0.06); moreover detection of anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in the patient than in the control group. Both these conditions correlate with a recent EBV infection or reactivation. The data suggest that EBV, particularly during acute infection or in its reactivation phase, could be involved in the ANA and ENA autoantibody formation.