Researchers have engineered human cardiac tissues to reveal how autoantibodies in patients with systemic lupus erythematosus may directly cause myocardial injury, shedding light on previously elusive mechanisms of heart damage, according to a recent study.

Myocardial involvement is present in 25% to 50% of patients with lupus. The researchers aimed to understand how autoantibodies in these patients may contribute to myocardial damage, focusing particularly on patients with and without clinical evidence of myocardial involvement. The study provided insights into the pathophysiology of myocardial injury in lupus using engineered human cardiac tissue models. 

In the study, published in Nature Cardiovascular Research, the researchers engineered human cardiac tissues that were exposed to immunoglobulin G (IgG) from patients with lupus. They found that IgG from patients with increased myocardial inflammation showed greater binding to apoptotic cells under stress conditions. Conversely, IgG from patients with systolic dysfunction exhibited more binding to live cardiomyocytes. 

This binding was associated with alterations in cellular composition, impaired calcium handling, and changes in gene expression, suggesting a pathogenic role of these autoantibodies in myocardial function. The study also found a strong positive correlation between IgG binding levels—measured as mean fluorescence intensity in engineered cardiac tissues—and the degree of myocardial inflammation, as indicated by standardized uptake values in 18F-FDG PET/CT imaging (r² = 0.88, P = .0002).

Further analysis through RNA sequencing revealed 707 differentially expressed genes (DEGs) between tissues treated with IgG from Myo+SD+ patients and those from Myo− patients, and 1,035 DEGs between tissues treated with IgG from Myo+SD+ patients and Myo+SD− patients. Additionally, surface biotinylation and mass spectrometry analysis revealed 27 unique surface proteins in cardiomyocytes and 72 unique surface proteins in cardiac fibroblasts, with 143 proteins shared between the two cell types.

Phage immunoprecipitation sequencing further identified distinct autoantibody profiles among patient subgroups, highlighting four potential pathogenic autoantibodies that may directly influence myocardial injury. 

Full disclosures can be found in the published study.