NEW DIRECT ASSAY OF FREE PROTEIN-S ANTIGEN APPLIED TO DIAGNOSIS OF PROTEIN-S DEFICIENCY

Congenital deficiencies of protein S (PS) are associated with thrombop hilia. Their characterization and classification have been hampered by the complex physiology of the protein C-protein S system and the poor standardization and reliability of laboratory assays. The free active form of protein S is usually determined by immunoassay using polyclon al antibodies in the plasma supernate after polyethyleneglycol (PEG) p recipitation. A new one step ELISA using two monoclonal antibodies spe cific for distinct epitopes of the free form of protein S has been dev eloped for the direct measurement of free PS in untreated plasma. We h ave tested two ELISA assays for free PS. One assay was based on the PE G precipitation (Asserachrom PS(R), Stage, Asnieres, France) whereas t he other was a one step ELISA assay (Asserachrom(R) free PS, Stage). V alues were obtained in 35 PS deficient patients recruited among 500 co nsecutive patients evaluated by the laboratory for diagnosis of congen ital disorders of coagulation. Values were compared to those obtained in 50 patients with no PS deficiency matched for age and sex with the PS deficient patients as well as in 33 normal subjects and in 12 pregn ant women. Strong correlation was found between the two tests (r = 0.8 1, p < 10(-5)) in the entire population (n = 130), as well as in the s eparate groups. The new one step ELISA was more accurate than the PEG free PS determination. Determination of PS activity and antigens allow ed us to separate quantitative and qualitative deficiencies. Among the qualitative deficiencies, isolated decrease in PS activity was the mo st frequent defect observed (66%). This fact questions the substitutio n of PS activity assays by the one step antigenic free PS ELISA assay.