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CLINICAL RESEARCH: CARDIOMYOPATHY

Fc Receptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy

Alexander Staudt, MD^_*, Petra Eichler, PhD, Christiane Trimpert, Msc^_*, Stephan B. Felix, MD^_*,_* and Andreas Greinacher, MD

^_* Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität, Greifswald, Germany

Manuscript received July 20, 2006; revised manuscript received October 13, 2006, accepted November 6, 2006.

^_* Reprint requests and correspondence: Dr. Stephan B. Felix, Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Fr.-Loefflerstr. 23a, 17475 Greifswald, Germany. (Email: felix{at}uni-greifswald.de).

Objectives: The purpose of this study was to investigate how cardiac autoantibodies might contribute to cardiac dysfunction in patients suffering from dilated cardiomyopathy (DCM).

Background: In the majority of DCM patients, it is possible to detect antibodies with negative inotropic effect on cardiomyocytes. The manner in which these antibodies impair cardiac function is poorly understood.

Methods: Immunoglobulin (Ig)G was prepared from plasma of 11 DCM patients containing antibodies that induced a negative inotropic effect on cardiomyocytes. We analyzed the effects of antibodies/IgG fragments on calcium transients and on systolic cell shortening of adult rat cardiomyocytes and investigated the dependency of these effects on potential cardiomyocyte Fc receptors.

Results: In contrast to control subjects, intact IgG from DCM patients reduced calcium transients and cell shortening of cardiomyocytes. The F(ab')₂ fragments of these antibodies did not induce these effects but inhibited the functional effects of DCM-IgG of the respective patients' IgG. These effects were also inhibited by Fc fragments of normal IgG. Reconstitution of the Fc part by incubation of cardiomyocytes with DCM-F(ab')₂ fragments followed by goat-anti-human-F(ab')-IgG again induced reduction of cell shortening and of calcium transients. In rat and human ventricular cardiomyocytes, Fc receptors IIa (CD32) were demonstrated by immunofluorescence.

Conclusions: Our findings indicate that DCM-IgG-F(ab')₂ bind to their cardiac antigen(s), but the Fc part might trigger the negative inotropic effects via the newly detected Fc receptor on cardiomyocytes. These results point to a novel potential mechanism for antibody-induced impairment of cardiac function in DCM patients.

Abbreviations and Acronyms   DCM = dilated cardiomyopathy   Ig = immunoglobulin

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