THE RELATIONSHIP BETWEEN PLASMA MICROPARTICLES, PROTEIN-S AND ANTICARDIOLIPIN ANTIBODIES IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

The high prevalence of free protein S deficiency in human immunodefici ency virus (HIV)-infected patients is poorly understood. We studied 38 HIV seropositive patients. Free protein S antigen values assayed usin g the polyethylene-glycol precipitation technique (PEG-fS) were statis tically lower in patients than in controls. These values using a speci fic monoclonal antibody-based ELISA (MoAb-fS) and the values of protei n S activity (S-act) were not statistically different between patients and controls. C4b-binding protein values were not different from cont rol values. In patients, PEG-fS values were lower than MoAb-fS values. Ten patients had a PEG-fS deficiency, 4 patients had a MoAb-fS defici ency and 8 had a S-act deficiency. Protein S activity and MoAb-fS were lower in clinical groups with poor prognosis and in patients with AID S but PEG-fS was not. A trend for reduced S-act/MoAb-fS ratios was obs erved In patients. PEG-fS was negatively correlated with anticardiolip in antibody liters whereas MoAb-fS was not. The plasma of PEG-fS defic ient HIV-patients contained high amounts of flow cytometry detectable microparticles which were depleted from plasma by PEG precipitation, T he microparticles were partly CD42b and CD4 positive but CD8 negative. These microparticles were labelled by an anti free protein S monoclon al antibody. The observed differences between MoAb-fS and PEG-fS value s were correlated with the amount of detectable plasma microparticles, just like the differences between MoAb-fS and S-act. Plasma micropart icles correlated with anticardiolipin antibody titers. In summary. fre e protein S antigen in HIV infected patients is under-estimated when t he PEG precipitation technique is used due to the presence of elevated levels of microparticles that bind protein S. The activity of free pr otein S is also Impaired by high levels of microparticles. The prevale nce of free protein S deficiency in HN positive patients is lower than preciously published (4/38, similar to 10%) and is correlated with po or prognosis. By implication, use of a PEG precipitation technique mig ht give artefactually low free protein S antigen values in other patie nt groups if high numbers of microparticles are present. In HIV patien ts, high titers of anticardiolipin antibodies are associated with high concentrations of cell-derived plasma microparticles.