Sugars make the difference - Glycosylation of cardiodepressant antibodies regulates their activity in dilated cardiomyopathy.

ABSTRACT

BACKGROUND: Cardiodepressant antibodies contribute to cardiac dysfunction in dilated cardiomyopathy (DCM). Changes in immunoglobulin G (IgG) glycosylation modulate the activity of various autoimmune diseases and influence disease activity as well as severity of various autoimmune diseases. We hypothesized that alterations in IgG glycosylation are involved in the disease course of DCM. METHODS AND RESULTS: IgG glycosylation was analyzed in plasma samples of 50 DCM patients using a lectin-based ELISA. Negative inotropic (cardiodepressant) activity (NIA) of antibodies was assessed by measuring the effect of purified DCM-IgG on the shortening of isolated rat cardiomyocytes by means of a video-edge detection system. IgG obtained from plasma of healthy blood donors served as control. DCM-IgG contained significantly less sialic acid (-25%) and galactose (-16%; both P < 0.001), but showed no significant differences in core-fucosylation compared to controls. Interestingly, IgG with NIA displayed a lower percentage of sialylation (-16%, P < 0.001) core-fucosylation (-15%, P = 0.015) and galactosylation (-10%, P = 0.129) than IgG without NIA. The extent of NIA was directly associated with IgG sialylation (r = 0.68; P < 0.001) and galactosylation (r = 0.37; P = 0.001). CONCLUSION: Reduced sialylation and galactosylation of IgGs enhances their cardiodepressant activity in DCM indicating that changes in IgG glycosylation may be involved in the pathogenesis of DCM.