Abstract 13547: Role of Foxp3 Regulatory T Cell and Adiponectin Expression in Functional Recovery of Fulminant Myocarditis Patients Necessitating Ventricular Assist Device
Background: It has been shown that initiation and progression of fulminant myocarditis are associated with viral infection and/or immune disorders. Foxp3 regulatory T cell (Treg), which is characterised by Foxp3/CD3 double positive lymphocytes, has been reported to play a protective role against immune-associated acute inflammatory disorders in a variety of organs, while adiponectin is known to be a negative regulator of activated T cell and acute inflammation. We hypothesized that functional prognosis of fulminant myocarditis might be determined by recruitment of Treg and accumulation of adiponectin into the cardiac tissue.
Methods: A consecutive series of 15 patients with fulminant myocarditis necessitating ventricular assist device (VAD) were studied. Of them, 5 patients showed a functional recovery sufficient to explant VAD (median VAD support 34 days, ranging 11 to 93 days), whereas 10 patients required prolonged VAD support due to persistent functional deterioration (median VAD support 312 days, ranging 9 to 1099 days). Distribution of Foxp3 Treg, and adiponectin were immunohistologically evaluated in transmural cardiac specimens that were sampled at VAD implantation.
Results: Although the number of CD3 T cell (83±71 cells/mm2 vs 258±193 cells/mm2, P=0.09), Foxp3 Treg (6±2 cells/mm2 vs 4±4 cells/mm2, P=0.28) , or CD68 macrophage (595±489 cells/mm2 vs 1541±967 cells/mm2, P=0.06) infiltrated into the heart were not significantly different between the groups, Foxp3/CD3 ratio was significantly greater in the recovery group than the non-recovery group (8±3% vs 3±4%, P=0.036). In addition, the Foxp3/CD3 ratio were significantly correlated with improvement in left ventricular EF (R=0.86, P=0.0004). Immunohistological study demonstrated binding of adiponectin to Foxp3 Treg in both the groups, suggesting that adiponectin play a role in the infiltration of Foxp3 Treg into myocarditis tissues.
Conclusion: Foxp3 Treg and adiponectin were recruited into the cardiac tissue of fulminant myocarditis, and higher Foxp3/CD3 ratio was associated with recovery of cardiac function in patients requiring VAD. These results suggest that recruitment of Foxp3 Treg and/or adiponectin may be a possible therapeutic target in fulminant myocarditis.
- © 2012 by American Heart Association, Inc.