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Circulating heart-reactive antibodies in patients with myocarditis or cardiomyopathy
D A Neumann1, C L Burek, K L Baughman
1Department of Immunology and Infectious Diseases, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Insights
Heart-reactive antibodies are common in myocarditis and cardiomyopathy. Western immunoblotting identified specific heart antigens, aiding in diagnosing these conditions.
Area of Science:
- Cardiology
- Immunology
- Pathogenesis of Heart Disease
Background:
- Heart-reactive antibodies are prevalent in myocarditis and cardiomyopathy.
- Their specific antigenic targets and role in disease pathogenesis remain understudied.
Purpose of the Study:
- To systematically characterize circulating heart autoantibodies in patients with myocarditis or idiopathic cardiomyopathy.
- To identify specific heart antigens recognized by these autoantibodies using Western immunoblotting.
Main Methods:
- Sera from patients with myocarditis (n=17), idiopathic cardiomyopathy (n=71), and healthy volunteers (n=15) were analyzed.
- Indirect immunofluorescence detected high-titer immunoglobulin G (IgG) antibody activity.
- Western immunoblotting assessed IgG reactivity against normal human heart extract, enumerating antigens and estimating molecular weights.
Main Results:
- High-titer IgG activity was found in 59% of myocarditis and 20% of cardiomyopathy samples.
- No significant difference in the mean number of heart antigens recognized across groups.
- Increased prevalence of antibodies to 190-199 kDa antigens in low-titer myocarditis serum.
- High-titer cardiomyopathy serum showed increased antibodies to 40-49 kDa and 100-109 kDa antigens compared to normal serum.
Conclusions:
- Western immunostaining can identify specific heart autoantibodies.
- This technique shows potential for substantively aiding in the identification of patients with myocarditis or cardiomyopathy.
Abstract:
Heart-reactive antibodies are commonly observed in patients with myocarditis or cardiomyopathy. Such antibodies may be important in the pathogenesis of these disorders, yet the specific antigens recognized have not been studied systematically. This report characterizes circulating heart autoantibodies from patients with myocarditis (n = 17) or idiopathic cardiomyopathy (n = 71) and from healthy volunteers (n = 15). Indirect immunofluorescence demonstrated that high titer (greater than or equal to 1:20) immunoglobulin G (IgG) antibody activity occurred in 59% of the myocarditis samples, 20% of the cardiomyopathy samples and none of the normal samples. All samples were tested by Western immunoblotting for IgG activity against a normal human heart extract. The number of antigens recognized by each sample was enumerated and the molecular weight of each antigen estimated; the prevalence of reactivity against antigens in selected molecular weight classes was determined. There was no difference in the mean number of heart antigens recognized by serum from each group. For most weight classes, prevalence either did not differ significantly among the various groups or subgroups or was greatest among samples from healthy volunteers. Prevalence of reactivity with 190 to 199 kilodalton (kd) antigens was greatest (p less than 0.05) among low titer serum samples from patients with myocarditis. High titer cardiomyopathy serum differed from normal serum by an increased (p less than 0.05) prevalence of antibodies to 40 to 49 and 100 to 109 kd antigens. These results suggest that western immunostaining may ultimately contribute substantively to identifying patients with myocarditis or cardiomyopathy.