Abstract 17422: The Role of Changes in IgG-glycosylation in the Pathogenesis of DCM: A Link Between Terminal Sialic Acid and the Negative Inotropic Activity of DCM-IgG
Background: There is evidence that circulating cardiodepressive antibodies play a role in cardiac dysfunction of patients with dilated cardiomyopathy (DCM). We have previously demonstrated that purified antibodies obtained from DCM patients induce in the majority of the cases negative inotropic effects on isolated rat cardiomyocytes. Moreover, the strength of the negative inotropic activity (NIA) correlated with improvement after immunoadsorption therapy (IA). In rheumatoid arthritis, not only autoantibodies itself play an important role in the pathogenesis of the disease, but also changes in Fc-glycosylation of these antibodies. Referring to this, we investigated the glycan structures of IgG purified from plasma of control subjects and from plasma of DCM patients at baseline before IA and six month after IA.
Method and Results: Detection of terminal sialic acid (tSA) was carried out by using biotinylated SNA (Sambucus nigra-Agglutinin) in a lectin-based ELISA. (lectins: sugar-binding proteins)
At baseline, the fluorescence data revealed a significant decrease by approx. 20% in detectable tSA of IgG from DCM patients compared to controls. Here, IgG with NIA [defined as reduction in cell shortening of isolated rat cardiomyocytes of greater than 10%] contained significantly less tSA (-26% vs. control) whereas for affinity-purified DCM-IgG (300 μg/ml) that did not affect the contractility of cardiomyocytes the tSA content was similar to that of controls. Interestingly, the NIA of purified IgG correlated significantly (p = 0.001) with the fluorescence intensities for tSA (r = 0.7405).
Six month after IA, we found a significant increase in the amounts of tSA in DCM-IgG (p=0.001 vs. baseline) to a level similar to that of controls. Thus, DCM-IgG with the lowest levels of tSA at baseline exhibited the highest relative increase of tSA six months after IA (r=-0.7309). Moreover, the increase of tSA in DCM-IgG came along with a significant reduction in the NIA of these IgG on isolated rat cardiomyocytes (p = 0.001).
Conclusion: Our results indicate that there is a link between the content of tSA in the glycan structures of IgG from DCM patients and the NIA of these IgG molecules on isolated cardiomyocytes.
- © 2013 by American Heart Association, Inc.