Serological and clinical findings in patients with serological evidence of reactivated Epstein-Barr virus infection.

IgM directed against Epstein-Barr virus (EBV) early antigen (IgM-EA) has been established as an early marker of EBV infection and IgG directed against Epstein-Barr virus nuclear antigen I (IgG-EBNA-1) as a late marker. Simultaneous seropositivity to IgM-EA and IgG-EBNA has therefore been proposed as indicating reactivation of latent EBV infection. We have studied 191 patients with serological evidence of reactivated EBV infection with regard to clinical presentation, antibodies directed against EBV viral capsid antigen (IgM-VCA, IgG-VCA), cytomegalovirus (IgM-CMV), human herpesvirus 6 (IgM-HHV-6). IgM rheumatoid factor (IgM-RF), anti-nuclear or anti-cytoplasmic antibodies (ANA/ACA), and total IgM. The clinical manifestations varied considerably, but a diagnosis was established in 121 of the patients. The diversity of the clinical diagnosis probably reflects common reasons for requesting an EBV serological test rather than clinical manifestations of reactivated EBV infection. Only 5.8% of the patients with "serological EBV reactivation" gave a positive result for IgM-VCA. We conclude that "serological EBV reactivation" does not represent an entity relating to clinical manifestations, but probably reflects a non-specific activation of the immune system.