Abstract 13059: Immuno Quantification of a Cytotoxic T-Cell Immunoresponse in Stellectomy Specimens of Patients Treated for Severe Ventricular Arrhythmias
Introduction Long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are electrical diseases characterized by stress-induced ventricular arrhytmias. Unbalanced autonomic innervation of the heart might trigger arrhythmic events thus suggesting left stellectomy as treatment for patients (pts) resistant to pharmacological drugs. We analysed the pathological characteristics of stellate ganglia resected from LQTS/CPVT pts with intractable arrhythmias.
Design Stellate ganglia were retrieved from 10 pts (7F, 3M, mean age 20.7±15.5 yrs) with either LQTS (n=5) or CVPT (n=5). Control stellate ganglia were obtained from 4 accidently deceased patients (1F, 3M, mean age 20.5±3.8 yrs). Sections were immunostained with antibodies against CD3 (pan T cell), CD8 (cytotoxic T cells, CTL's), GranzymeB (activated CTL's), CD20 (B cells), CD68 (macrophages) and HLA-DR antigens. Morphometry was performed counting intraganglional immunopositive cells/mm2.
Results Stellate ganglia of all 10 LQTS/CVPT pts revealed mild but distinct inflammatory infiltrates composed of T-lymphocytes and macrophages in all 10 cases, which were diffusely spread, but also clustered in small foci in close apposition to or even inside ganglion cells, interpreted as T cell-mediated ganglionitis. Morphometrical analysis showed that 75-80% of CD3+ T-cells were CD8+ CTL's, of which many contained GranzymeB+ granules. Specifically, CD3+ cell counts were 500±315 in cases vs 226±58 in control ganglia (p value=0.03), and CD8+ cell counts were 385.2±194 vs 175±68 in controls (p=0.01). In contrast, the numbers of CD4+ T-helper cells and CD20+ B-cells were very low (28±41 and 17±27, respectively). Quantitative comparison of ganglion-related T cells in the two groups of pts (LQTS and CPVT) showed in CPVT absolute numbers of T cell about twice than LQTS, even if the difference was not significant.
Conclusions. A low grade CTL-mediated ganglionitis occurs in stellate ganglia of all 10 severely symptomatic LQTS/CVPT patients. Cytotoxicity towards ganglion cells may boost adrenergic activity, and thus electrical instability in these patients who are genetically predisposed to arrhythmias.
- © 2011 by American Heart Association, Inc.