Cardiomyopathy – an approach to the autoimmune background

Publication date: Available online 2 February 2017
Source:Autoimmunity Reviews
Author(s): Niels-Peter Becker, Johannes Müller, Gerd Wallukat, Ingolf Schimke
Autoimmunity is increasingly accepted as the origin or amplifier of various diseases. In contrast to classic autoantibodies (AABs), which induce immune responses resulting in the destruction of the affected tissue, an additional class of AABs is directed against G-protein-coupled receptors (GPCRs; GPCR-AABs). GPCR-AABs functionally affect their related GPCRs for activation of receptor mediated signal cascades. Diseases which are characterized by the presence of GPCR-AABs with evidence for disease-specific pathogenic activity could be named "functional autoantibody disease".We briefly summarize here the historical view on autoimmunity in cardiomyopathy, followed by an approach to the mechanistic autoimmunity background. Furthermore, autoantibodies with outstanding importance for cardiomyopathies as a functional autoantibody disease, such as GPCR-AABs, and mainly those directed against the beta1-adrenergic and muscarinic 2 receptor autoantibodies, were introduced. Anti-cardiac myosin and anti-cardiac troponin autoantibodies, as further potential players in autoimmune cardiomyopathy, were additionally taken into account. The basic view on the autoantibodies, their related receptor interactions and pathogenic consequences were presented.Focused specifically on GPCR-AABs, "pros and cons" of assays such as indirect assays (functional changes of cells preparations were monitored after GPCR-AAB receptor binding) and direct assays based on the ELISA technologies (GPCR epitope mimics for GPCR-AAB binding) were critically discussed.Last but not least, treatment strategies for "functional autoantibody disease", such as for GPCR-AAB removal (therapeutic plasma exchange, immunoadsorption) and in vivo GPCR-AAB attack such as intravenous IgG treatment (IVIG), B-cell depletion and GPCR-AAB binding and neutralization, are critically reflected with respect to their patient benefits.



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