An Engineered Human Cardiac Tissue Model Reveals The Potential Contribution Of Systemic Lupus Erythematosus Autoantibodies To Myocardial Injury

A considerable number of patients with systemic lupus erythematosus (SLE) develop myocardial injury. SLE patients have highly heterogenous populations of autoantibodies that may contribute to cardiac disease pathogenesis and heterogeneity; however, little is known about their direct role in myocardial injury. Here, we engineered a model of matured human cardiac tissue and used it to study SLE induced myocardial injury. To this end, we cultured tissues with immunoglobulin G (IgG) from SLE patients with and without myocardial injury. We found that IgG binding levels differed between patient groups and correlated with measures of myocardial inflammation and systolic function. Interestingly, IgG from a subset of patients with systolic dysfunction exerted functional effects on our model system in the absence of immune cells, suggesting a direct contribution to myocardial injury. This was demonstrated by altered calcium handling and cellular composition, impaired cellular respiration, and distinctive patterns of gene expression determined by RNA sequencing. We further harnessed this model to identify potential disease-contributing autoantibodies. We propose that this model can be used to improve risk stratification and therapeutic strategies for SLE patients with myocardial injury.