Potential role of humoral immunity in cardiac dysfunction of patients suffering from dilated cardiomyopathy

Abstract

This research was conducted to evaluate the role played by the humoral immune system in cardiac dysfunction among dilated cardiomyopathy (DCM) patients, as enabled by immunoadsorption therapy (IA) that effectively removes functionally active cardiac autoantibodies from plasma. Various circulating autoantibodies have been detected among patients suffering from DCM. Before IA, antibodies were purified from plasma of 45 DCM patients (left ventricular ejection fraction [LVEF] <30%). We analyzed the functional effects of antibodies (300 mg/l) on calcium transients and on systolic cell shortening in adult rat cardiomyocytes. After this in vitro analysis, IA was performed in four courses at one-month intervals until month 3. Antibodies from 29 patients induced a reduction (>10%) in calcium transients (mean reduction: -16.5 +/- 1.9%) and a simultaneous reduction (>10%) of cell shortening (mean reduction: -21.2 +/- 1.8%) on cardiomyocytes (p < 0.001) (cardiodepressant group). Antibodies from 16 patients did not significantly influence calcium transients and cell shortening (<10%) (non-cardiodepressant group). During the first IA course, the cardiodepressant group demonstrated an acute increase in cardiac index (CI) from 2.2 +/- 0.1 l/min/m(2) to 2.9 +/- 0.1 l/min/m(2) (p < 0.001). In the non-cardiodepressant group, hemodynamics did not significantly change throughout three months. After three months before the final IA course (prolonged effects), the CI was 2.1 +/- 0.1 l/min/m(2) in the non-cardiodepressant group and 2.9 +/- 0.1 l/min/m(2) in the cardiodepressant group (p < 0.001). After three months LVEF increased only in the cardiodepressant group: from 20.8 +/- 1% to 30.5 +/- 1% (p < 0.01). In the majority of DCM patients, disturbances of humoral immunity with production of cardiodepressant antibodies may play a functional role in cardiac dysfunction. Evidence of cardiodepressant antibodies predicts hemodynamic benefits during IA.