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. 1999 Feb;115(2):236-47.
doi: 10.1046/j.1365-2249.1999.00807.x.

IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease

P Skyllouriotis  1 , M Skyllouriotis-Lazarou, S Natter, R Steiner, S Spitzauer, S Kapiotis, P Valent, A M Hirschl, S E Guber, G Laufer, G Wollenek, E Wolner, M Wimmer, R Valenta
Affiliations

IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease

P Skyllouriotis et al. Clin Exp Immunol. 1999 Feb.

Abstract

Studies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.

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Figures

Fig. 1
Fig. 1
Coomassie blue-stained SDS–PAGE containing human cellular (epithelial cells: A 431; endothelial cells: HUVEC) and tissue-derived (heart, skeletal muscle) protein extracts. M represents the molecular weight marker. Molecular weights are displayed in kD on the left.
Fig. 2
Fig. 2
IgG reactivity to nitrocellulose-blotted human epithelial (a), endothelial (b), myocard (c) and skeletal muscle (d) protein extracts. Epithelial, endothelial, and skeletal muscle extracts were exposed to sera from cardiomyopathy (CMP) patients (children/juveniles, lanes 1–28; adults, lanes 1–8) and from healthy individuals (lanes 1–9). Myocard extracts (c) were probed with the same sera and in addition with nine sera from patients with coronary heart disease and one additional healthy person. Lanes B represent the buffer control without addition of serum. Molecular weights are displayed in kD. The large arrow in (c) indicates the position of anti-myosin immunoreactivity.
Fig. 3
Fig. 3
Purified cardiac muscle myosin inhibits serum IgG reactivity of a cardiomyopathy (CMP) patient to Western-blotted heart muscle-derived myosin. Serum from a CMP patient which was preabsorbed with purified cardiac myosin (lane a) or bovine serum albumin (BSA) (lane b) was exposed to nitrocellulose-blotted human heart muscle extract. Molecular weights are displayed on the left. The large arrow indicates the position of cardiac myosin.
Fig. 4
Fig. 4
IgG reactivity of sera from cardiomyopathy (CMP) patients (children/juveniles: lanes 1–28, adults: lanes 1–8) and from healthy individuals (lanes 1–4) with nitrocellulose-blotted Streptococcus pyogenus protein extracts. Lane B represents the buffer control without addition of serum. Molecular weights (kD) are displayed on the left.
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