Abstract 13404: Serum Anti-Intercalated Disk Autoantibodies in Arrhythmogenic Right Ventricular Cardiomyopathy are Autoimmune Markers Associated with Pathogenic Desmosomal Mutations
Objective: Serum anti-heart autoantibodies (AHA) and anti-intercalated disk autoantibodies (AIDA) are organ and disease-specific autoimmune markers in myocarditis, dilated cardiomyopathy and their relatives. Biopsy-proven myocarditis is frequently reported in arrhythmogenic right ventricular cardiomyopathy (ARVC) but its etiopathogenetic significance remains poorly understood. It is also unknown whether AHA and AIDA are autoimmune markers in ARVC with known desmosomal gene mutations.
Methods: We assessed serum AHA and AIDA in 164 ARVC patients (pts) or relatives (90 male, mean age 34±17 years), of whom 30 ARVC index pts, 110 affected relatives (AR) and 24 asymptomatic unaffected relatives (UR). ARVC pts, AR and UR met the 2010 revised ESC Task force diagnostic criteria. AHA and AIDA were detected by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical and genetic diagnosis. Control groups for AHA and AIDA included sera from patients with non-inflammatory cardiac disease (NICD)(n=160, 80 male, aged 37±17), with ischemic heart failure (n=141, 131 male, age 51±12) and normal blood donors (n=270, 123 male, aged 35±11). Cascade mutation screening of five ARVC genes, e.g. plakoglobin (JUP), desmoplakin (DSP), plakophilin-2 (PKP-2), desmoglein- 2 (DSG-2), desmocollin-2 (DSC-2) was obtained in 137 of the 164 pts.
Results: The frequencies of AHA and of AIDA were higher (31%; 15%) in ARVC, than in NICD (1%; 4%), ischemic heart failure (1%; 2%) or normal subjects (2.5%; 0%)(p=0.0001; p=0.0001 respectively). Of the 137 genotyped, 40 (29%) pts were gene-positive, PKP2 and DSP mutations were most frequent (19, 14% and 9, 6% respectively), 6 cases (4%) had double mutations. Positive AIDA status in pts was associated with PKP-2 (p=0.02), and DSP mutations (p=0.03), and with lower left ventricular ejection fraction (p=0.03).
Conclusion: The finding of serum AIDA suggests autoimmune involvement in the pathogenesis of desmosomal mutation associated ARVC.
- © 2011 by American Heart Association, Inc.