Inhibition of Protein S by Autoantibodies in Patients with Acquired Protein S Deficiency

Abstract

SummaryThis study was undertaken to analyze antibodies to protein S (PS) in patients with an acquired PS deficiency. Plasma from symptomatic patients with acquired (n = 14) or congenital (n = 10) PS deficiency and 10 healthy donors was screened for PS antibodies by immunoblotting and for anti-phospholipid antibodies. PS antibodies (IgG) were detected in five of the patients with acquired PS deficiency. These antibodies belonged to the G1 and G4 immunoglobulin subclasses. IgG fractions from the same 5 patients were shown to inhibit PS activity. The inhibition of PS activity by the 5 IgG fractions was shown to be time-and dose-dependent and was abolished following incubation with purified PS, while no effect was found after absorption with cardiolipin micelles. In addition, anticardiolipin monoclonal or human purified antibodies, failed to exert significant PS inhibition. These findings demonstrate that anti-PS antibodies are able to inhibit PS activity and that this is independent of anti-phospholipid antibodies. Given the clinical features of the patients, these antibodies should be regarded as an expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins.

Coagulation, inflammation, and apoptosis: different roles for protein S and the protein S–C4b binding protein complex

“…The antibodies, which are immunoglobulin G subclass and are independent of the antiphospholipid antibodies, inhibit PS activity and persist for about 3 months. 166 Autoantibodies against PS can also be found in antiphospholipid syndrome, and these seem to be associated with increased thrombotic risk when in combination with antibodies against ␤ 2 -glycoprotein I. 167 Indeed, anti-PS antibodies and acquired PS deficiency are common findings in SLE, 168 and a report has suggested that acquired PS deficiency may provoke a hyperinflammatory response.…”

Autoantibodies specific to a peptide of β2-glycoprotein I cross-react with TLR4, inducing a proinflammatory phenotype in endothelial cells and monocytes

“…[1][2][3] The aPLs recognize phospholipids, phospholipidbinding plasma proteins, and/or plasma protein-phospholipid complexes. Among the involved phospholipid-binding plasma proteins, which include prothrombin, 4 protein C, 5 and protein S, 6 ␤ 2 -glycoprotein I (␤ 2 GPI) is now recognized as the most relevant antigenic target for aPLs. 7 Anti-␤ 2 GPI Abs are composed of subpopulations that differ in their biologic activity and bind with different epitopes on the molecule.…”

Vimentin/cardiolipin complex as a new antigenic target of the antiphospholipid syndrome

“…[7][8][9][10][11][12][13][14] However, a seronegative catastrophic APS has been recently described. 32,33 In this study, we analyzed new possible antigenic target(s) of the antibodies that could be used to identify these patients.…”