Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same...

Patients with seropositive rheumatoid arthritis (RA) have elevated titers of precipitating antibody toward an antigen designated RA nuclear antigen (RANA). Anti-RANA reactivity has been associated with prior Epstein-Barr virus (EBV) infection. Using the protein blot technique, we have identified, in extracts of WI-L2, an EBV+ nonproducer B-lymphoblast line, a Mr 80,000 polypeptide that is reactive with anti-RANA-containing sera. This same polypeptide can be recovered from RANA precipitin bands. The Mr 80,000 polypeptide appears to be EBV-associated, as a homologous antigen was detected in two other EBV+ cell lines, Daudi and Raji, but was not present in three EBV- human cell lines tested, HeLa, BJAB, and Ramos. Anti-RANA antibodies and antibodies reactive with the Mr 80,000 polypeptide also appear coincidently in the sera of individuals exhibiting an EBV infection (infectious mononucleosis). Further analysis of the RANA-associated Mr 80,000 polypeptide suggested its identity with the previously recognized EBV-associated nuclear antigen designated EBNA. The Mr 80,000 antigen shares with EBNA the properties of being a heat-stable, DNA binding protein. EBNA is traditionally assayed by a complement fixation reaction and anti-Mr 80,000 antibodies were shown to be reactive when a complement fixation assay was used in the immunoblot. Finally, when the Mr 80,000 antigen was used to absorb an anti-RANA/anti-EBNA serum, both antibodies were reduced.