EXPRESSION OF bcl-2 IN RHEUMATOID ARTHRITIS

Since defective apoptosis has been suggested to play a role in the development of autoimmune diseases, we have investigated the expression of the proto-oncogene bcl-2 in patients with rheumatoid arthritis (RA). The expression of bcl-2 was studied in peripheral blood (PB) and synovial fluid (SF) lymphocytes and synovial tissues (ST) from patients with RA using immunohistochemistry, flow cytometry and nucleic acid hybridization. Patients with reactive arthritis (ReA) or osteoarthritis (OA) and healthy individuals were used as controls. The expression of bcl-2 protein in PB lymphocytes and the expression of bcl-2 mRNA in PB mononuclear cells (PBMC) was similar in healthy controls and patients with RA. However, bcl-2 protein expression was significantly reduced in SF lymphocytes when compared to PB lymphocytes. Similar results were observed with lymphocytes from patients with ReA, and irrespective of whether total lymphocytes, T cells or different T-cell subsets were studied. In the synovial sections, the expression of bcl-2 was restricted to lymphocytes, and bcl-2+ cells were observed in the majority of samples from patients with RA, OA and ReA. These data indicate that the expression of bcl-2 is not increased in the lymphocytes or ST derived from patients with RA. Instead, decreased expression of bcl-2 protein in SF lymphocytes compared to PB lymphocytes was demonstrated. We suggest that bcl-2 does not play a significant role in the pathogenesis of RA.