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Evidence of Anti-Cardiac Antibody Deposition in End-Stage Failing Myocardium: A Potential Contributor to Disease Progression

      Introduction

      Various reports have raised the possibility of humoral immune responses as contributors for the progression of heart failure. Previous studies have focused analysis on serum from patients with non-ischemic cardiomyopathy (NICM) and documented circulating antibodies against a variety of cardiac proteins. However, no evidence exists in the literature on whether they localize to failing myocardium.

      Hypothesis

      IgG and IgG3 are present in failing human myocardium.

      Methods

      Myocardium was obtained on 100 patients at the time of heart transplant or LVAD insertion following IRB approval. Samples were then fixed and embedded in paraffin following standard protocols. Sections were cut and stained using standard fluorescent immunohistochemistry techniques for antihuman IgG (Invitrogen) antibodies and IgG3 (SantaCruz Biotechnology) antibodies. Slides were analyzed by a pathologist who was blinded to the experimental conditions.

      Results

      The mean age was 55.4 ± 13 with 72% of the patients male. NICM was the etiology of heart failure in 51 patients and ICM in 49. IgG was present in 65% of the patients, and was primarily localized to the sarcolemma of the cardiomyocytes (Figure 1A). Within the NICM group, 71% of the patients were positive for IgG deposition, and of those 69% also showed the presence of IgG3. In the ICM group, 59% were positive for IgG, and within that group 59% were also IgG3 positive (Figure 1B and 1C).

      Conclusion

      In patients with end stage cardiomyopathy there is the presence of IgG and its subclass IgG3. There were more patients with NICM that had IgG and IgG3 when compared to the ICM group. The exact effect IgG has on the cardiomyocyte is unknown, but it's presence on the sarcolemma raises the possibility of direct effect on myocyte contraction. The presence of IgG3 suggests that it may have a role in complement activation that may also affect heart failure.
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