Plasma proteomics profiling of PD-1 inhibitor-associated myocarditis and acute myocardial infarction: A clinical and preclinical study

Immune checkpoint inhibitors (ICIs)-related myocarditis is a rare but severe side effect that is often accompanied by elevated levels of cardiac troponin I, making it difficult to distinguish from acute myocardial infarction (AMI). Our study aims to explore the differences in blood protein profiles between ICIs-related myocarditis and AMI, and to identify potential biomarkers. We performed plasma proteomics on 15 plasma samples from 5 pairs with ICIs-related myocarditis at treatment baseline and diagnosis, and 5 cases of AMI confirmed by coronary angiography. A total of 1521 plasma proteins were identified, with 1325 quantifiable plasma proteins across all 15 plasma samples. Our study observed that ICIs-related myocarditis group showed differential expressed protein (DEPs) involved in myocardial contraction, immunoregulation, proteasome, arginine and proline metabolism, and cysteine and methionine metabolism. We also identified that MYOM3, Galectin-1, and CSF1 are highly expressed in ICIs-related myocarditis compared with other groups by plasma proteomics analysis, and utilized more AMI plasma samples, as well as animal models of ICIs-related myocarditis and AMI to further validate these findings. These results have the potential to provide valuable predictive information for future clinical research.