Fc(gamma) receptors IIa on cardiomyocytes and their potential functional relevance in dilated cardiomyopathy.
OBJECTIVE
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(gamma) 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(gamma) receptor on cardiomyocytes. These results point to a novel potential mechanism for antibody-induced impairment of cardiac function in DCM patients.
Staudt
Alexander
A
Klinik für Innere Medizin B, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.
Eichler
Petra
P
Trimpert
Christiane
C
Felix
Stephan B
SB
Greinacher
Andreas
A
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002118:Calcium / Q000493:pharmacokinetics; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D016022:Case-Control Studies; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D017452:Receptors, IgG / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis; D013599:Systole
D015703:Antigens, CD; D001323:Autoantibodies; C052643:F(ab')2 receptor; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D002118:Calcium