HLA-G MOLECULES ARE COSTITUTIVELY EXPRESSED BY HUMAN SYNOVIAL FIBROBLASTS AND UP-MODULATED IN OSTEOARTHRITIS

Objective: HLA-G molecules are non classical HLA class I antigens expressed as membrane bound and soluble isoforms (sHLA-G) with a restricted tissue distribution and anti-inflammatory functions (1). Osteoarthritis (OA) is a complex degenerative disease that affects articular cartilage components and causes damage to the entire joint structure including synovium (2). Since inflammation is involved in the pathogenesis of OA, we have analyzed the expression and the production of HLA-G molecules in “in vitro” cultured synovial fibroblasts (SFs) from OA patients and control subjects. Design: We have analyzed the levels of sHLA-G1 and HLA-G5 isoforms by immunoenzymatic assay (ELISA) in the SFs culture supernatants from six OA patients and six control subjects during a 70 day “in vitro” cultures in the presence and in the absence of lipopolysaccharide (LPS) or recombinant IL-10 (rIL-10). We have confirmed HLA-G modulation by cytofluorimetry and immunofluorescence. Results: Data in ELISA have demonstrated the spontaneous production of sHLA-G molecules by both OA and control SFs. The expression has been confirmed by cytofluorimetry and immunofluorescence. OA SFs produce higher levels of sHLA-G1 and HLA-G5 molecules during the first 23 days of culture in comparison to control SFs. The sHLA-G1 levels further increase over the next 20 days of “in vitro” culture. Atfer LPS and rIL-10 treatments, sHLA-G secretion increases in a similar manner in both OA and control SFs. Conclusions: The production of sHLA-G1 molecules, constitutively expressed by control and OA SFs, is significantly higher in OA than in control SFs, suggesting that these molecules represent a possible molecular target to counteract the synovial joints inflammation