Résumé
To elucidate the involvement of adipocytokines "Adiponectin" in the pathogenesis of rheumatoid arthritis [RA] by measuring serum and synovial fluid levels of adiponectin in RA patients and also by evaluating its expression in RA synovial tissue to find out its possible role in disease activity and severity in order to throw light on possible new strategy in the management of RA. Twenty RA patients and ten subjects with acute post traumatic knee effusion - who served as a control group-were recruited for this study. Serum adiponectin levels were measured using enzyme linked immunosorbent [ELISA]. Synovial fluid [SF] levels of adiponectin, IL-6 and pro MMP-1 were measured by ELISA. Modified disease activity score [DAS] and Larsen score were assessed in RA patients. Synovial tissue [ST] specimens were obtained from control subjects and RA patients. These specimens were assessed immunohistochemically for adiponectin and graded in a semiquantitative scale. Serum adiponectin was significantly raised in RA patients compared to controls [p<0.05]. There was a highly statistically significant increase in SF adiponectin, SF Pro MMP-1, ST adiponectin expression in RA patients compared to controls [p<0.01], while there was a significant increase in SF IL-6 in RA patients compared to controls [p<0.05]. SF adiponectin correlated positively with each of ST adiponectin expression, SF IL-6, SF pro MMP-1 [p<0.01]. A highly significant positive correlation was found between SF levels of adiponectin and each of DAS and Larsen score [p<0.01]. Adiponectin is expressed in the RA synovium and it stimulates the production of key mediators of destructive arthritis, IL-6 and pro MMP-1, so targeting the proinflammatory cascade of adiponectin may represent an exciting new therapeutic tool in RA
Sujets)
Humains , Mâle , Femelle , Adiponectine/sang , Synovie , Interleukine-6/sang , Immunohistochimie , Membrane synoviale/anatomopathologieRésumé
Psoriatic arthritis [PsA] is a chronic inflammatory arthritis characterized by infiltration of the skin and joints with activated T lymphocytes. The latter have been implicated in both the initiation and maintenance of inflammatory lesions at these sites and it is mediated by the local production and secretion of chemotactic cytokines. To evaluate the role of monocyte chemotactic protein-1 [MCP-1] in the immunopathogenesis of PsA. Also, to find out whether evidence exists for a causal relationship between MCP-1 levels in synovial fluids and T cells recruitment to lesional sites during acute and chronic synovitis and its relation to disease activity in psoriatic arthritis patients. Thirty PsA patients were recruited for this study. They were subdivided into two groups: Group I: 15 patients with synovitis less than 6 months' duration [acute PsA]. Group II: 15 patients with synovitis more than 6 months' duration [chronic PsA]. The clinical activity of the disease was assessed by using modified disease activity score 28 [DAS28]. Their results were compared to 15 healthy age and sex matched volunteers [group III]. Peripheral blood [PB] and synovial fluid [SF] were obtained from PsA arthritis patients; also PB was obtained from normal controls. Immune cell populations in PB and SF samples were assessed with immunofluorescent labeling and flow cytometry, levels of soluble MCP-1 were determined in PB and SF samples with quantitative ELISA. DAS28 was significantly higher in group I [acute PsA] patients than group II [chronic PsA patients] [p<0.01]. CD4+, CD8+ T cells were significantly elevated in SF as compared to PB of acute but not chronic PsA patients and the majority of these cells expressed CD45RO [p<0.01]. Plasma MCP-1 levels were elevated in PsA [whether acute or chronic] relative to normal controls [p<0.01]. SF MCP-1 levels were significantly higher than paired plasma samples in acute PsA patients only [p<0.01]. A highly significant positive correlation was observed between MCP-1 levels in SF and DAS28 and also with T cell numbers in SF of acute PsA patients [p<0.01]. The elevated concentration of MCP-1 is concomitant with T cell infiltration in SF of acute PsA patients. This suggests that MCP-1 mediated chemotaxis is involved in the recruitment of T lymphocytes particularly memory cells into the synovial fluid in PsA during acute synovitis which is associated clinically with severely active disease and thus could be considered as an early inflammatory marker in acute PsA