Immunoglobulin M (IgM) autoantibodies to oxidation-specific epitopes (OSE) 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 lower risk of acute myocardial infarction (AMI) in humans. IgM to malondialdehyde-low density lipoprotein (MDA-LDL), phosphocholine-modified bovine serum albumin (PC-BSA), IgM apolipoprotein B100-immune complexes (ApoB-IC) and a peptide mimotope of malondialdehyde (MDA) were measured within 24 hours of first AMI in 4559 patients and 4617 age and sex-matched controls in the Pakistan Risk of Myocardial Infarction Study. Adjustment was made for sex, age, smoking, hypertension, diabetes, LDL-C, HDL-C, and triglycerides. Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (95% CI) for AMI. All four IgM OSE were lower in AMI versus controls (p<0.001 for all). Males, smokers and individuals with hypertension and diabetes had lower levels of all 4 IgM OSE compared to unaffected individuals (p<0.001 for all). Compared to the lowest quintile, the highest quintiles of IgM MDA-LDL, PC-BSA, ApoB-IC, and MDA mimotope P1 had lower OR of AMI: OR (95% (CI)] 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 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 provide clinically meaningful information and support the hypothesis that higher levels of IgM OSE may be protective against AMI.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
