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Original

Pathological autoantibodies in cardiomyopathy

, , , &
Pages 454-461 | Received 03 Feb 2008, Accepted 05 Mar 2008, Published online: 07 Jul 2009
 

Abstract

Myocardial dilatation and dysfunction in the absence of significant coronary heart disease has been termed “idiopathic” dilated cardiomyopathy (iDCM), which—according to the 1995 task force report on the classification of cardiomyopathies—besides genetic, toxic or infectious causes also includes immune-mediated heart muscle damage in the spectrum of putative DCM etiologies. Incremental research on this topic particularly in the past few years has significantly contributed evidence to the hypothesis that autoimmune reactions against certain myocyte antigens may play a pivotal role in the initiation and/or progression of DCM. Recent transfer experiments in animals (mostly rodents) performed by various groups throughout the world and some preliminary clinical data even indicate that a few of these autoantibodies are indeed “pathogenic”, inferring that they can actually cause cardiac dysfunction and heart failure by their own. Dependent on the individual genetic predisposition such harmful autoimmune reactions are supposed to emerge as a consequence of heart muscle damage induced by viral triggers, ischemia or exposure to cardiotoxins leading to myocyte apoptosis (and/or necrosis) and subsequent liberation of a “critical amount” of self-antigens previously hidden to the immune system.

The following article will summarize the so far available evidence for an implication of a confined number of harmful autoantibodies directed against specific cardiac antigens in the pathogenesis of DCM.

Abbreviations
ADP/ATP=

adenosine di-/tri-phosphate

Beta-1-AR=

beta1-adrenergic receptor

Beta1-ECII=

second extracellular loop of the beta1-AR

cAMP=

(cyclic) adenosine mono-phosphate

CaMKII=

Ca2 + /calmodulin-dependent protein kinase II

CHOP=

C/EBP-homologous protein

CM=

cardiac myosin

cTnI=

cardiac troponin I

DCM=

dilated cardiomyopathy

ELISA=

enzyme-linked immunoabsorbent assay

FRET=

fluorescence resonance energy transfer

GRP78=

glucose-regulated protein 78

ICM=

ischemic cardiomyopathy

LVED=

left ventricular end-diastolic diameter (echocardiography)

PKA=

cAMP-dependent protein kinase A

MAPK=

mitogen-activated protein kinase

Abbreviations
ADP/ATP=

adenosine di-/tri-phosphate

Beta-1-AR=

beta1-adrenergic receptor

Beta1-ECII=

second extracellular loop of the beta1-AR

cAMP=

(cyclic) adenosine mono-phosphate

CaMKII=

Ca2 + /calmodulin-dependent protein kinase II

CHOP=

C/EBP-homologous protein

CM=

cardiac myosin

cTnI=

cardiac troponin I

DCM=

dilated cardiomyopathy

ELISA=

enzyme-linked immunoabsorbent assay

FRET=

fluorescence resonance energy transfer

GRP78=

glucose-regulated protein 78

ICM=

ischemic cardiomyopathy

LVED=

left ventricular end-diastolic diameter (echocardiography)

PKA=

cAMP-dependent protein kinase A

MAPK=

mitogen-activated protein kinase

Acknowledgements

Parts of the data have been presented at the 1st International Symposium on Auto-immunity in Cardiomyopathy and Heart Failure, Goeteborg, Sweden (29–30.11.2007). Our work is currently supported by the Deutsche Forschungsgemeinschaft (Grant DFG/Ja 706/2-4), the IZKF Würzburg (Grant E32), the German Competence Net of Heart Failure (CNHF, TP 6b), and the Bundesministerium für Bildung und Forschung (BMBF, GoBio-1/ FKZ 0315031).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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