Characterization of the Serological Response in Man to the Latent Membrane Protein and the Six Nuclear Antigens Encoded by Epstein-Barr Virus

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Abstract
A total of 116 sera from healthy individuals and from patients with Burkitt''s lymphoma (BL), nasopharyngeal carcinoma (NPC) or rheumatoid arthritis (RA) were studied with respect to antibody responses to each of the seven known transformation-associated Epstein-Barr virus (EBV)-encoded antigens [latent membrane protein (LMP) and six nuclear proteins (EBNAs 1 to 6)]. The antibodies were detected using modified standard immunoblotting techniques. Antibodies to LMP were detected for the first time in sera from 6/27 (22%) healthy, EBV-immune individuals (seropositive for the viral capsid antigens). An increased incidence of anti-LMP antibodies was found in EBV-immune sera from patients with BL (17/24 positive; 71%), NPC (21/33; 64%), and RA (16/21; 76%). Antibodies to EBNA 1 were detected in all EBV-immune sera at a standard 1:20 dilution. Antibodies to the other EBNAs were detected in only a proportion of these sera (20 to 95%) at the same dilution. Only minor disease-associated differences in the incidence of these antibodies were observed, the most consistent being that RA sera had a higher incidence of antibodies to EBNAs 2 to 6 compared with healthy controls. Testing of the sera at a 1:100 dilution suggested that there were some disease-related differences in the titres of anti-EBNA antibodies. At this serum dilution, a reduced incidence of antibodies to EBNA 2 was seen in NPC (6/31) compared with RA (18/19) and healthy EBV-seropositives (16/26); antibodies to EBNA 3 were detected at an increased incidence in BL (8/15) and NPC (16/31) compared with control sera (7/26); antibodies to EBNA 4 were detected at increased incidence in BL (5/15) and RA (6/19) compared with control sera (1/26); and antibodies to EBNA 6 were detected at increased incidence in NPC (19/31) and RA (7/19) compared with control sera (3/26).