DIRECT EVIDENCE FOR THE EXPRESSION OF MULTIPLE ENDOGENOUS RETROVIRUSES IN THE SYNOVIAL COMPARTMENT IN RHEUMATOID-ARTHRITIS

Objective. Circumstantial evidence links retroviruses (RVs) with human autoimmune diseases, The aim of the present study was to obtain direc t evidence of RV gene expression in rheumatoid arthritis (RA). Methods . Synovial samples were obtained from patients with RA, patients with osteoarthritis (OA), and normal control subjects, Reverse transcriptio n-polymerase chain reaction (RT-PCR) was performed using synovial RNA and primers to conserved sequences in the polymerase (pol) genes of kn own RVs. Results. PCR products (n = 857) were cloned and sequenced, Mu ltiple pol transcripts, many with open reading frames, were expressed in every sample, Sequences were aligned and classified into 6 families (F1-F6) that contained 33 groups of known and unknown endogenous RVs (ERVs), each distinguished by a specific, deduced peptide motif, The f requency of sequences in each family was similar between RA, OA, and n ormal synovial tissue, but differed significantly in RA synovial fluid cells, F1 sequences (undefined, but related to murine and primate typ e C RVs) were lower in frequency, F2 (ERV-9-related), F4 (HERV-K-relat ed), and F6 (HERV-L-related) sequences were higher in frequency, and F 3 (RTVL-H-related) sequences were not detected, in the RA synovial flu id cells compared with the RA synovial tissues. Conclusion. Multiple E RVs are expressed in normal and diseased synovial compartments, but sp ecific transcripts can be differentially expressed in RA.