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Chlamydophila pneumoniae is an ubiquitous intracellular pathogen which causes acute respiratory diseases and may be associated with chronic inflammatory diseases including atherosclerosis, multiple sclerosis and arthritis. C. pneumoniae is rarely cultured from the synovial fluid or blood, and serology is seldom useful. So far most of the studies concerning the possible association between C. pneumoniae and arthritis have been made by molecular methods. Recent advances in the standardization of polymerase chain reaction techniques have shown to confirm a role of C. pneumoniae not only in reactive arthritis (ReA) but also in chronic arthritis. In this study, we investigated whether C. pneumoniae could be isolated in synovial fluid and PBMC specimens of patients with different forms of arthritis including ReA.Advanced PCR and Reverse transcriptase PCR techniques targeting different chlamydial genes associated to a novel culture method based on combination of additional centrifugation and extension of culture time, were applied to detect C. pneumoniae in 6 patients with chronic synovitis including one with Anchylosing Spondylitis and relapsing joint swelling. For this patient, serological, coltural as well as molecular assays did detect C. pneumoniae only. Particularly, a high expression of Heat shock protein 60 and 70 of C. pneumoniae was found in the PBMC and the synovial compartments, thus confirming the ability of C. pneumoniae to survive inside blood ad synovia in vital and metabolically active forms. By contrast, the selective decrease of MOMP and 16sRNA, leads to hypotesize a different expression of Chlamydophyla genes during the different phases of infection.