A Search for Rheumatoid Arthritis‐Associated Nuclear Antigen And Epstein‐Barr Virus Specific Antigens or Genomes in Tissues and Cells from Patients with Rheumatoid Arthritis

Abstract

Pannus extracts andor cells and tissues from rheumatoid arthritis (RA) patients and controls were tested for the presence of RA-associated nuclear antigen (RANA), anti-RANA, Epstein-Barr virus (EBVbspecific antigens, and EBV genomes. Using our present rather insensitive methods, RANA was rarely detected in RA pannus extracts or tissues, whereas anti-RANA was commonly found. EBV-specific antigens or genomes could not be detected in a limited number of tissues tested using our present methods. The data suggest that EBV may not be the primary event causing RA through direct infection and transformation of synovial tissues.Previous studies have demonstrated that patients with rheumatoid arthritis (RA) have elevated levels of antibody directed toward an antigen termed RA-associated nuclear antigen (RANA) (1,2). Other studies showed that RANA was associated with Epstein-Barr virus (EBV) infection (3). More recent

Lack of evidence for an involvement of Epstein-Barr virus infection of synovial membranes in the pathogenesis of rheumatoid arthritis

“…The in situ hybridization and immunohistochemistry techniques used to detect EBV infection gave consistently positive results in appropriate controls and have been widely used previously by ourselves and others (13,14). Our results are supported by studies that have demonstrated a lack of detectable EBV genomes in RA tissues using Southern blot hybridization and reassociation kinetics (10,11). It could be argued that because of the low sensitivity of these techniques, EBV infection in a small proportion of cells may have been missed in these studies.…”

“…These results are at variance with previous studies that have failed to detect EBV DNA in synovial membranes from RA patients (10,11). To clarify this issue, we have undertaken a comparative study of synovial membrane biopsy samples from patients with RA and from those with other joint diseases, with the use of highly sensitive in situ hybridization and immunohistochemistry techniques.…”

Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

“…Nevertheless, direct evidence for the involvement of EBV in the pathogenesis of RA is still lacking. A recent study by Alspaugh et al (9) failed to find increased levels of EBV DNA within RA synovial membranes. However, low amounts of viral DNA would not be detected using these methods of hybridization.…”

Lytic Epstein‐Barr virus infection in the synovial tissue of patients with rheumatoid arthritis

“…However, there have been conflicting reports concerning the existence of EBV in the synovial tissue of RA patients (22)(23)(24)(25)(26)(27)(28). Recently, Scotet et al demonstrated that a large fraction of T cells infiltrating affected joints of RA patients recognize 2 EBV-encoded proteins, BZLF1 and BMLF1 (29).…”