Viruses and lymphocytes in rheumatoid arthritis. II. Examination of lymphocytes and sera from patients with rheumatoid arthritis for evidence of retrovirus infection.

Abstract

summARY The possible involvement of retroviruses in the aetiology of rheumatoid arthritis (RA) was investigated. Retrovirus antigens were not expressed on rheumatoid synovial and peripheral blood lymphocytes as judged by membrane immunofluorescence, radioimmunoassay, and complement-mediated cytotoxicity. The specific antiretroviral (anti-RD-144 and anti-SSAV) sera used in this study were produced in rabbits immunised with viral antigens grown in a homologous system (rabbit cells and medium supplemented with normal rabbit serum), avoiding non-specific immunofluorescence previously detected with donated antiretroviral sera. Immune complexes lodged in the rheumatoid synovial membranes did not contain, and other cells within the membranes did not express, retroviral antigens. Antibodies cross-reacting with primate retrovirus antigens were sought in sera from patients with 'autoimmune' diseases by means of solid phase radioimmunoassay. There were no retrovirus antibodies in the 3 groups of patients studied, that is, those with rheumatoid arthritis, systemic lupus erythematosus, and with non-RA conditions. Absorption of rheumatoid factor did not alter this conclusion. These results give little support to the hypothesis that activation of endogenous human retroviruses or an infection with horizontally transmitted retroviruses is associated with the rheumatoid process.

Viruses and lymphocytes in rheumatoid arthritis. I. Studies on cultured rheumatoid lymphocytes.

“…More recently, however, viral mRNA of SP104 was not detected in either human or canine SLE tissues by sensitive methods of nucleic acid hybridisation (Quimby et al, 1978), a result which is hard to reconcile with the previous data. In the accompanying paper Hart et al (1979) describe experiments to detect retrovirus antigens on the membranes of synovial lymphocytes by radioimmunoassay and immunofluorescence with uniformly negative results. However, possibly it was necessary to culture the cells to induce the virus, and indeed, as in the case of xenotropic viruses, which will replicate only in cells of a different species, it might have been necessary to use methods of induction, fusion with permissive cells, and cocultivation before virus is isolated.…”

“…Goat antisera to and SSAV (Tween-ether disrupted) were originally obtained from Dr J. Gruber (National Cancer Institute), and used at 1/10 dilution in PBS, supplemented with 2% fetal calf serum (PBS-FCS). Rabbit antisera were later prepared to RD-1 14 and SSAV antigens (Hart et al, 1979) and used at a dilution of 1/20 in indirect immunofluorescence tests on acetone-fixed cells grown on cover-slips (Schmidt et al, 1966;Lennette et al, 1967). Horse anti-human lymphocyte serum was kindly donated by Dr K. James.…”

“…Both share various antigenic determinants, such as p30 and gp69-71, with other mammalian species and should therefore be able to detect any retroviral antigens in human cells. Originally goat antisera to the 2 viruses, which had been Tween-ether disrupted, were used, but later antisera prepared in rabbits were used (Hart et al, 1979). In no case was there any suggestion of positive immunofluorescence.…”

“…The cells were subsequently examined for virus by labelling with 3H-uridine, the culture supernatant being assayed for reverse transcriptase activity, and finally for the presence of virus-coded proteins in the cell membranes by immunofluorescence. In the accompanying paper the results of testing lymphocytes for the presence of viral antigens on their membranes, including retrovirus antigens by immunofluorescence and radioimmunoassay, are described (Hart et al, 1979).…”

Search for viruses in rheumatoid macrophage-rich synovial cell populations.

“…This loss of immunoregulatory control could be due to a viral infection of the immune effector cells (Messner, 1974). Recent virological studies on lymphocytes from synovial fluids and membranes have included an Accepted for publication March 16, 1979 Correspondence to Dr M. Norval examination for retroviruses, but these were not shown to be present by methods such as nucleic acid hybridisation, fusion, and cocultivation with cells permissive for primate retroviruses, immunofluorescence, and radioimmunoassay Hart et al, 1979).…”