Key result
Anti-cardiac IgG deposition is present in ~71% of end-stage failing myocardium, correlating with disease duration.
Why the study?
Previous studies focused on circulating serum antibodies, leaving little evidence on whether anti-cardiac antibodies or activated complement components are deposited in end-stage failing myocardium.
Is there evidence of anti-cardiac antibody and complement deposition in end-stage failing human myocardium compared to donor controls?
Observational (n=140)
Is there evidence of anti-cardiac antibody and complement deposition in end-stage failing human myocardium compared to donor controls?
Anti-cardiac antibodies and complement activation are frequently deposited in end-stage failing myocardium regardless of etiology, suggesting a role for humoral immunity in heart failure progression.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Complement activation, IgG deposition, and expression of the proinflammatory cytokine TNF-alpha has been described in patients with DCM”
Supports immunomodulatory research in end-stage HF; leaves open whether tissue antibody deposition drives progression or reflects epiphenomenon.
AIMS: Various reports have raised the possibility of humoral immune responses as contributors for the progression of heart failure. Previous studies, however, have focused on the analysis of serum and documented circulating antibodies against a variety of cardiac proteins. However, there is little evidence on whether anti-cardiac antibodies are deposited in end-stage failing myocardium. Our objective was to determine whether or not there was evidence of deposition of anti-cardiac antibodies and/or activated complement components in end-stage failing human myocardium. METHODS AND RESULTS: Myocardial samples were obtained from 100 end-stage heart failure patients and 40 donor control biopsies. Sections were cut and stained using standard fluorescent immunohistochemistry techniques with anti-human immunoglobulin G (IgG), IgG3, and C3c. Gel electrophoresis and protein identification by mass spectrometry were used to confirm the presence of IgG and its antigen. Immunoglobulin G was localized to the sarcolemma in 71% of patients, 48% of those being positive for the subtype IgG3. The proportion of patients with ischaemic heart disease that was positive for IgG was 65% and among those with non-ischaemic aetiologies was 76%. In a subgroup analysis, the presence of IgG and its subunits were confirmed by mass spectrometry and adenosine triphosphate synthase β subunit identified as an antigen. Complement was activated in 31% of all patients. The presence of IgG, IgG3, and C3c was directly correlated with the length of disease (r = 0.451, P = 0.006). CONCLUSION: Evidence of anti-cardiac antibodies and complement activation was found in a large number of patients with end-stage cardiomyopathy regardless of the aetiology. Adenosine triphosphate synthase appears to be a new prominent antigenic stimulus; but more interestingly, the simultaneous co-existence of activated complement components suggests that this humoral mechanism may participate in disease progression.
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Youker et al. (2013) conducted an observational in End-stage heart failure (n=140). End-stage heart failure vs. Donor control biopsies was evaluated on Deposition of Immunoglobulin G (IgG) in the sarcolemma. Anti-cardiac antibody deposition (IgG) was found in 71% of end-stage failing myocardium samples, directly correlating with the length of disease (r = 0.451, P = 0.006).
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