A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes

Paul C Dimayuga; Kuang-Yuh Chyu; Xiaoning Zhao; Jianchang Zhou; Nicole Wai Man Lio; Fernando Chernomordik; Daniel Berman; Prediman K Shah; Bojan Cercek

doi:10.1016/j.jacbts.2024.04.012

A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes

JACC Basic Transl Sci. 2024 Jul 22;9(7):877-887. doi: 10.1016/j.jacbts.2024.04.012. eCollection 2024 Jul.

Authors

Paul C Dimayuga¹, Kuang-Yuh Chyu¹, Xiaoning Zhao¹, Jianchang Zhou¹, Nicole Wai Man Lio¹, Fernando Chernomordik¹, Daniel Berman², Prediman K Shah¹, Bojan Cercek¹

Affiliations

¹ Oppenheimer Atherosclerosis Research Center, Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
² Departments of Imaging and Medicine and Burns and Allen Research 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.

Keywords: cathelicidin; immune complex; immunothrombosis; platelet.