IDENTIFICATION AND FUNCTIONAL IMPORTANCE OF PLASMA KALLIKREIN IN THE SYNOVIAL-FLUIDS OF PATIENTS WITH RHEUMATOID, PSORIATIC, AND OSTEOARTHRITIS

Objectives-To determine and identify, unequivocally, if plasma kallikr ein (PK) is present in the synovial fluid of patients with rheumatoid (RA), psoriatic (PA) and osteo (OA) arthritis, and to consider its fun ctional importance in the inflamed joint. Methods-Therapeutically aspi rated synovial fluids (pooled and individual samples, n = 66) were obt ained from patients with arthritis. In addition, serum (n = 14) was co llected from RA patients, and saliva (n = 10) and urine (n = 10) from normal individuals. Enzymic (amidase) and immunoreactive activities of PK and its precursor, prokallikrein (PPK), were determined. The prese nce of PK was assessed by incubation with soya bean trypsin inhibitor (SBTI), and by adsorption with anti-PK antibody linked to Sepharose. A n enzyme-linked immuno-sorbant assay (ELISA) for PK was developed for quantitative measurement of total PK in biological fluids. Enhancement of the PK dose-response by RA synovial fluid made it necessary to rem ove RF from synovial fluids before determination of PK by ELISA. Resul ts-Amidase activity was demonstrated in synovial fluid pools and shown to be inhibited completely by SBTI, and removed by prior treatment wi th anti-PK Sepharose. Total PK activity (PK + PPK) from individual syn ovial fluid specimens did not differ significantly between patients wi th RA (median activity 76 mU/g protein), PA (80 mU/g protein) or OA (6 0 mU/g protein). Similar results were obtained when active measured. N o PK alone was correlation was found between active PK or total PK val ues and the severity score for individual joints. Most of the measured immunoreactivity was removed by adsorption with anti-PK antibody link ed to Sepharose. Conclusions-The results support the hypothesis that p lasma kallikrein is present in synovial fluid. The enzyme may be impor tant in the pathogenesis of inflamed joints.