Subclass reactivity to Epstein-Barr virus capsid antigen in primary and reactivated EBV infections

A new method for analysis of virus-specific Immunoglobulin G (IgG) subclasses was developed using indirect immunofluorescence. Three hundred thirty-three serum samples from patients with different types of Epstein-Barr virus (EBV)-associated diseases and healthy controls were examined for subclass distribution to the virus capsid antigen (EBV VCA). EBV-VCA-expressing cell preparations were incubated with patient serum followed by monoclonal antibodies to human IgG1 through IgG4 and labelled anti-mouse IgG. Virus-specific IgG1 was found to be the dominant antibody. The titers for IgG1 and total Ig to EBV VCA correlated well. EBV VCA-specific IgG2 was not found. EBV VCA-specific IgG3 in a titer of greater than or equal to 10 was found in 33% of healthy seropositive donors, in 97% of patients with suspected reactivated EBV infection, and in 100% of symptomatic patients with suspected reactivated EBV infection. EBV VCA specific IgG3 occurred in 90% of placebo-treated compared to 30% in long-term acyclovir-treated bone marrow transplant recipients, indicating more frequent reactivations in the former group. IgG4 to VCA was infrequently found in seropositive persons. In serum samples from patients with nasopharyngeal carcinoma and high EBV VCA Ig and IgA titers, IgG4 to VCA was always present. Analysis of EBV VCA specific IgG subclasses seems to be valuable for the diagnosis of reactivated EBV infection.