Abstract 1947: Interferon-beta Treatment Improves Parvovirus B19-induced Vascular Damage And Normalises Numbers Of CD34+ KDR+-Progenitors In Patients With Parvovirus B19 Positive positive inflammatory cardiomyopthy
In the majority of patients with inflammatory cardiomyopthy, human parvovirus B19 (PVB19)-persistence can be detected. This vasculoptropic virus targets endothelial cells, thereby inducing microvascular damage and myocardial dysfunction. Interferon-β (IFN) had been shown to positively influence the outcome of patients with persistent viral myocarditis. We, therefore tested the hypothesis of a reduction of endothelial damage by IFN in patients with PVB19 persistence. Circulating mature apoptotic EC (CMAEC; CD45−/CD146+/vWF+/annexin-v+) and endothelial progenitor cells (EPC; CD34+/KDR+) were quantified from peripheral blood using FACS analysis in 10 controls and 9 patients with PVB19 before and after 6 month of 16 MioU IFN therapy. Endothelial dysfunction was measured by ultrasound using flow-mediated dilatation (FMD) of the forearm. Replication of PVB19 in cultivated endothelial cells (EC) was quantified by quantitative PCR of the non-structural protein (NS1) and the capsid protein (VP) before and after (100U/ml) IFN-β. When compared to controls, patients with PVB19 had significantly higher (p = 0.004) levels of CMAEC, that normalised after 6 month of IFN-β (0.06 ± 0.08% vs. 0.01 ± 0.006, p = 0.008). Similar improvement was shown for FMD (p = 0.02 vs. control; 6.3% vs. 13.6%, p = 0.02). CMAEC and FMD correlated inversely (r=0.7, p=0.02). There were significantly higher numbers of EPC in patients with persistent PVB19 before therapy (p = 0.03) compared to control subjects. Indeed, only patients with angina in their history showed a strong trend towards elevated levels of EPC (0.52 ± 0.48 vs. 0.01 ± 0.009%/PMNC, p = 0.059). After IFN therapy, EPC levels were normalised (p= 0.015). IFN suppressed PVB19 replication by 63% (p<0.05) in EC and increased their viability (p<0.05). Vascular damage, and specifically, endothelial cell apoptosis, in patients with PVB19 is reduced by immunomodulation with interferon-β. Increased mobilisation of EPC in patients with PVB19 myocarditis and angina normalises during therapy and functional impairment is reversed. Thus, for the first time we present a viral-induced modulation of endothelial damage and regenerative capacity.