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Abstract: SA-PO591

Platelet Activation Is Induced via Myeloperoxidase Production and Anti-Myeloperoxidase Antibodies Primed by Thrombin

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Author

  • Miao, Di, Peking University First Hospital, Beijing, China
Background

In addition to their central role in hemostasis and thrombosis, platelets involve in inflammatory responses. Anti-neutrophil cytoplasmic autoantibodies (ANCAs) directed to myeloperoxidase (MPO-ANCAs) are the main serological markers of ANCA-associated vasculitis.

Methods

Platelets were stimulated by purified total IgG and MPO-ANCA from patients with or without low doses of thrombin. The fragments from MPO-ANCAs, F(ab’)2 and Fc, were digested and isolated, then incubated with thrombin-primed platelets. The F(ab’)2 pull-downed proteins were analyzed using mass spectrometry. The concentration of MPO was detected in active platelets and AAV patients.

Results

The current study demonstrated that MPO-ANCAs caused normal human platelets to activate, primed by low doses of thrombin. Purified immunoglobulin G, MPO-ANCAs and their F(ab’)2 fragments evidently increased the CD62P expression of platelets compared with controls. The existence of MPO in platelets was confirmed with mass spectrometry technology, after analyzing the F(ab’)2 fragment pull-downed proteins. After thrombin priming, platelets not only expressed MPO on the surface with an activation-dependent manner, but also released the enzyme to extracellular space. These effects markedly enhanced the activation of platelets. Additionally, there was no apparently increased CD62P-expression on platelets in MPO-ANCAs group compared with controls when adding MPO inhibitor, proving that primed platelets have ANCA antigen at their surfaces interacting with the autoantibodies.

Conclusion

These findings suggest a previously unappreciated character for platelets as immune cells and the autoantibodies-induced activation in an acute inflammatory disease.