The levels of soluble granzyme A and B are elevated in plasma and synovialfluid of patients with rheumatoid arthritis (RA)

Cytotoxic cells possess specialized granules which contain perforin and a g roup of serine proteinases termed granzymes. Granzyme-positive cells have b een identified in synovial fluid and tissue of patients with RA, where they may play an important role as mediators of granule-mediated apoptosis, ext racellular proteolysis, and cytokine induction. The aim here was to define further the involvement of cytotoxic cells in RA. Plasma and synovial fluid samples from the knee joint were obtained from 31 RA patients. The disease controls included 20 osteoarthritis (OA) patients and 10 reactive arthriti s (ReA) patients. A recently developed capture ELISA was used to detect sol uble granzymes A and B in all patients. Compared with OA and ReA disease co ntrols, markedly increased levels of soluble granzymes A and B were detecte d in both plasma and synovial fluid of RA patients (P < 0.00001). When valu es for soluble granzymes A and B in plasma and synovial fluid were used sim ultaneously as independent variables, logistic regression analysis indicate d that a diagnosis of RA could be predicted correctly in 84% of the RA pati ents and a diagnosis of non-RA in 90% of the controls. The markedly elevate d levels of soluble granzymes A and B in plasma and synovial fluid of RA pa tients strongly suggest that cytotoxic cells are active participants in the pathogenesis of RA. Moreover, the results suggest that measurement of gran zymes may assist the laboratory evaluation of patients with arthritis. Larg er studies in patients with early disease may clarify the role of this test system in differential diagnosis.