👩🔬👨🔬Autoantibodies directly affect heart function in lupus patients
Myocardial involvement occurs in 25–50% of patients with systemic lupus erythematosus (SLE), including those without symptoms, and can result in myocardial inflammation with ventricular dysfunction, progression to heart failure and high rates of mortality.
• A team of researchers report that autoantibodies alone directly affect heart function in lupus patients.
• They engineered millimeter-sized cardiac tissues from healthy adult human stem cells and and cultured them with IgG from patients with SLE, with and without myocardial involvement.
• The binding patterns of the patients' autoantibodies to heart tissue depend on the type and severity of their myocardial damage.
IgG from patients with elevated myocardial inflammation exhibited increased binding to apoptotic cells within cardiac tissues subjected to stress, whereas IgG from patients with systolic dysfunction exhibited enhanced binding to the surface of live cardiomyocytes
• A subset of patients with severe myocarditis had unique autoantibody populations that primarily targeted dying cardiac cells, whereas patients with weakened heart pump function had autoantibodies that mostly targeted the surface of live cells. Functional assays and RNA sequencing revealed that, in the absence of immune cells, IgG from patients with systolic dysfunction altered cellular composition, respiration and calcium handling.
• The study also identified four such autoantibodies that may directly affect the heart muscle. Phage immunoprecipitation sequencing (PhIP-seq) confirmed distinctive IgG profiles between patient subgroups.
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