High immunoglobulin-M levels to oxidation-specific epitopes are associated with lower risk of acute myocardial infarction.

Immunoglobulin M (IgM) autoantibodies to oxidation-specific epitopes (OSEs) can be present at birth and protect against atherosclerosis in experimental models. This study sought to determine whether high titers of IgM titers to OSE (IgM OSE) are associated with a lower risk of acute myocardial infarction (AMI) in humans. IgM to malondialdehyde (MDA)-LDL, phosphocholine-modified BSA, IgM apolipoprotein B100-immune complexes, and a peptide mimotope of MDA were measured within 24 h of first AMI in 4,559 patients and 4,617 age- and sex-matched controls in the Pakistan Risk of Myocardial Infarction Study. Multivariate-adjusted logistic regression was used to estimate odds ratio (OR) and 95% confidence interval for AMI. All four IgM OSEs were lower in AMI versus controls (P < 0.001 for all). Males, smokers and individuals with hypertension and diabetes had lower levels of all four IgM OSE than unaffected individuals (P < 0.001 for all). Compared to the lowest quintile, the highest quintiles of IgM MDA-LDL, phosphocholine-modified BSA, IgM apolipoprotein B100-immune complexes, and MDA mimotope P1 had a lower OR of AMI: OR (95% confidence interval) of 0.67 (0.58-0.77), 0.64 (0.56-0.73), 0.70 (0.61-0.80) and 0.72 (0.62-0.82) (P < 0.001 for all), respectively. Upon the addition of IgM OSE to conventional risk factors, the C-statistic improved by 0.0062 (0.0028-0.0095) and net reclassification by 15.5% (11.4-19.6). These findings demonstrate that IgM OSE provides clinically meaningful information and supports the hypothesis that higher levels of IgM OSE may be protective against AMI.
Competing Interests: Conflict of interest S. T and J. L. W. are co-inventors and receive royalties from patents owned by University of California San Diego (UCSD) and are co-founders and have an equity interest in Oxitope, Pharmaceuticals and Kleanthi Diagnostics. Although these relationships have been identified for conflict-of-interest management based on the overall scope of the project, the research findings included in this publication may not necessarily relate to the interests of the above companies. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. S. T. has a dual appointment at UCSD and Ionis Pharmaceuticals. J. L. W. is a consultant to Ionis Pharmaceuticals. The other co-authors have nothing to disclose.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)