TY - JOUR
T1 - High proportion of patients with end-stage heart failure regardless of aetiology demonstrates anti-cardiac antibody deposition in failing myocardium
T2 - Humoral activation, a potential contributor of disease progression
AU - Youker, Keith A.
AU - Assad-Kottner, Christian
AU - Cordero-Reyes, Andrea M.
AU - Trevino, Alejandro R.
AU - Flores-Arredondo, Jose H.
AU - Barrios, Roberto
AU - Fernandez-Sada, Evaristo
AU - Estep, Jerry D.
AU - Bhimaraj, Arvind
AU - Torre-Amione, Guillermo
PY - 2014/4/21
Y1 - 2014/4/21
N2 - 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.
AB - 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.
KW - Antibodies
KW - ATP synthase
KW - Autoimmunity
KW - Heart failure
KW - Myocardium
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U2 - 10.1093/eurheartj/eht506
DO - 10.1093/eurheartj/eht506
M3 - Article
C2 - 24375073
AN - SCOPUS:84899504803
SN - 0195-668X
VL - 35
SP - 1061
EP - 1068
JO - European heart journal
JF - European heart journal
IS - 16
ER -