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A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes
Paul C Dimayuga1, Kuang-Yuh Chyu1, Xiaoning Zhao1
1Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Abstract:
The cathelicidin antimicrobial peptide LL-37 is a self-antigen in neutrophil extracellular traps that provokes autoantibody responses in autoimmune/autoinflammatory conditions. LL-37 immunoglobulin (Ig) G autoantibody levels were measured in subjects with and without atherosclerotic cardiovascular disease assessed using the coronary artery calcium score, in patients who had a future myocardial infarction and in a cohort of acute coronary syndrome (ACS) patients. LL-37 IgG levels were not associated with coronary artery calcium score, but future myocardial infarction patients had significantly higher LL-37 IgG at baseline. Reduced LL-37 IgG in ACS was associated with increased LL-37 IgG-immune complex. ACS plasma increased activated CD62P+ platelets from healthy donors mediated in part by LL-37 IgG-immune complexes and platelet Fc gamma receptor 2a.
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