High-Avidity Antithrombin Antibodies Distinguish APS from SLE/aPL+ Patients

Strategic Insights -

Researchers in Los Angeles, California conducted a study to characterize the interaction between procoagulant and/or anticoagulant serine proteases and human monoclonal IgG antiphospholipid antibodies (aPL) and polyclonal IgG derived from patients with the antiphospholipid syndrome (APS). The study found that sequence changes in human aPL are important in determining their ability to bind procoagulant and anticoagulant/fibrinolytic serine proteases. The researchers discovered that mean IgG antithrombin levels were significantly elevated in patients with APS and in SLE patients with aPL but no APS (SLE/aPL+) compared to healthy controls. However, anti-activated protein C levels were not increased in these patients. The study also found that IgG purified from patients with APS displayed higher avidity for thrombin and significantly inhibited antithrombin inactivation of thrombin compared with IgG from SLE/aPL+ patients.

Key Takeaways:

  • Sequence changes in human aPL are crucial in determining their ability to bind procoagulant and anticoagulant/fibrinolytic serine proteases.
  • Mean IgG antithrombin levels were significantly elevated in patients with APS and in SLE patients with aPL but no APS (SLE/aPL+) compared to healthy controls.
  • Anti-activated protein C levels were not increased in patients with APS or SLE/aPL+.
  • IgG purified from patients with APS displayed higher avidity for thrombin and significantly inhibited antithrombin inactivation of thrombin compared with IgG from SLE/aPL+ patients.
  • High-avidity antithrombin antibodies, which prevent antithrombin inactivation of thrombin, distinguish patients with APS from SLE/aPL+ patients.
  • The high-avidity antibodies may contribute to the pathogenesis of vascular thrombosis in APS.

Statistics:

  • 5 human monoclonal IgG were tested for binding to protein C, activated protein C, plasmin, factor VIIa (FVIIa), FIX, FIXa, and FXII.
  • 32 patients with APS, 29 patients with systemic lupus erythematosus (SLE), and 22 healthy controls had serum levels of antithrombin compared.
  • Mean IgG antithrombin levels were significantly elevated in patients with APS and in SLE patients with aPL but no APS (SLE/aPL+) compared to healthy controls.
  • Anti-activated protein C levels were not increased in patients with APS or SLE/aPL+.

Sources:

  • Lambrianides, A., et al. (2011). Interactions of Human Monoclonal and Polyclonal Antiphospholipid Antibodies With Serine Proteases Involved in Hemostasis. Arthritis and Rheumatism, 63(11), 3512-3521.
  • Systemic Lupus Erythematosus.
  • Biotech Week editors from staff and other reports.