Granulocyte elastase as a new biochemical marker in the diagnosis of chronic joint diseases

Abstract

Human granulocyte elastase (EC 3.4.21.37) is released from granulocytes in large amounts in chronic inflammatory joint diseases and is therefore of special pathogenic and diagnostic importance. In order to examine the diagnostic significance of this enzyme as a clinico-chemical parameter, we determined the concentration of granulocyte elastase in complex with alpha 1-proteinase inhibitor by an enzyme immunoassay in synovial fluids and plasma of patients with chronic joint diseases. In inflammatory synovial fluids the concentration of complexed elastase correlates well with the granulocyte number and may increase to an extremely high level. In 90% of patients with manifest rheumatoid arthritis increased elastase levels are also observed in the plasma, probably due to the large gradient between the synovial fluid and plasma concentration, whereas in osteoarthrosis normal plasma concentrations were observed. Thus, these results indicate that normal plasma concentrations in patients with chronic joint diseases exclude the diagnosis of rheumatoid arthritis with high probability. The simultaneous determination of complexed elastase in plasma and synovial fluid improves the nosological differentiation of chronic joint diseases. Elastase activity on a specific chromogenic substrate, which was found in many inflammatory synovial fluids, is mainly attributed to elastase alpha 2-macroglobulin complexes. In some purulent synovial fluids, however, we were able to detect free elastase, which has been shown to play an important role in the destruction of articular cartilage.

Plasma and synovial fluid levels of granulocytal elastase-α-1-protease inhibitor complex in patients with rheumatoid arthritis

“…The level of EIC in the plasma of patients with RA was shown to be significantly higher than that in the plasma of healthy controls (P<0.01) as previously reported [32][33][34][35]. Furthermore, the level of EIC in the patients with MRA was significantly higher than that in patients with RA (P<0.05; Table 1).…”

Neutrophil function in pregnancy and rheumatoid arthritis

“…Together with elastase—a proteolytic enzyme stored in the azurophil granules—high concentrations of lactoferrin are evident in affected joints,40 41 and raised circulating levels have been shown in RA 42. Strong correlations with elastase-proteinase inhibitor complex and C reactive protein measurements of disease activity have advanced lactoferrin as a possible marker for neutrophil dependent inflammation in RA.…”

Predominant Role of Neutrophils in the Inactivation of α2‐Macroglobulin in Arthritic Joints

“…Alternatively, neutrophilic proteinases leaking from the joints may also have contributed to intravascular consumption of a2M. Elevated plasma levels of elastase-a,AT in RA have been reported in several studies (54)(55)(56)(57), and it has been suggested that this measurement would be useful in differentiating between RA and OA (57). Our findings support this notion: Plasma levels of elastase-a, AT were significantly increased in patients with RA, as compared with the levels in patients with OA and in normal controls (Table 3).…”