Circulating anti-endothelial cell autoantibodies in myocarditis: Novel immune markers of negative prognosis

In autoimmune disease some autoantibodies provide negative prognostic markers. Myocarditis may be immune-mediated; serum autoantibodies against various cardiac autoantigens are detected in a subset of patients. Methods. We studied 169 consecutive patients with biopsy-proven myocarditis (121 male, aged 36+/–18 years, left ventricular ejection fraction 43+/–14, all with angiographically normal coronary arteries). Serum at diagnosis was assessed for autoantibodies to cardiac endothelial cells (AECA) by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical diagnosis. AECA reacted with myocardium, but were unreactive with skeletal muscle. Control groups for AECA included sera from patients with non-inflammatory cardiac disease (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). AECA status was related to clinical and diagnostic features at presentation by univariate analysis. Survival free from death or heart transplantation (HTx) was calculated by the Kaplan-Meier method. Differences between actuarial curves between AECA positive and negative patients were analyzed by the log-rank test. Results. The frequency of AECA was higher (12%) in myocarditis than in non-inflammatory cardiac disease (1%), ischemic heart failure (1%) or normal subjects (2.5%)(p=0.0001). AECA positive status was associated with higher troponin I levels (p=0.0001) and nonsignificantly higher left ventricular enddiastolic pressure (p=0.06) at presentation. At last follow-up (mean 44+/–39 months) 141 patients were alive, 28 (27%) were dead or transplanted. 5-year survival free from death or HTx was lower in AECA positive vs. negative patients (67% vs. 91%, p=0.02, RR 3.8, 95%CI 1.1–12.6). Conclusion. The finding of AECA provides a negative serological predictor in biopsy-proven myocarditis and suggests that immune-mediated cardiac endothelial dysfunction may have a key role in disease progression.