February 15, 2014Open Access
View Full PaperT-Cell–Mediated Inflammatory Activity in the Stellate Ganglia of Patients With Ion-Channel Disease and Severe Ventricular Arrhythmias
Key Result
Patients with LQTS or CPVT had significantly higher levels of CD3+ and CD8+ T cells/mm2 in their stellate ganglia compared to healthy controls (P=0.0018 and P=0.0009, respectively).
Study Design
Type
Case-Control (n=22)
Structured PICO
Is there T-cell-mediated inflammatory activity in the stellate ganglia of patients with LQTS and CPVT compared to healthy controls?
P
Population
12 patients with LQTS or CPVT and serious arrhythmias and 10 accidently deceased controls whose stellate ganglia were analyzed for inflammatory activity.
E
Exposure
Histological, immunohistochemical, and molecular analysis of left stellectomy specimens.
C
Comparator
Control stellate ganglia obtained from 10 accidentally deceased patients (6 female; mean age, 35±17.6 years).
O
Outcome
Presence and quantification of inflammatory infiltrates (T cells and macrophages) in stellate ganglia.surrogate
The presence of T-cell-mediated ganglionitis in the stellate ganglia of LQTS and CPVT patients suggests that local inflammation may boost adrenergic activity and trigger arrhythmias in genetically predisposed individuals.
Main Result
p-value: P=0.0018 and P=0.0009
Abstract
BACKGROUND: Long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are electric diseases characterized by catecholamine-induced ventricular arrhythmias. Unbalanced autonomic innervation of the heart may trigger arrhythmic events and stellectomy is a treatment option for patients who are resistant to pharmacological drugs. We analyzed left stellectomy specimens of LQTS and CPVT patients for signs of inflammatory activity. METHODS AND RESULTS: Stellate ganglia were retrieved from 12 consecutive patients (8F; 4 mol/L; mean age, 23.4±17 years) with either LQTS (n=8) or CPVT (n=4) and serious arrhythmias. Control stellate ganglia were obtained from 10 accidently deceased patients (6F; 4 mol/L; mean age, 35±17.6 years). Sections were immunostained with antibodies against T cells (CD3, CD4, CD8, CD20, Granzyme B), CD68 (macrophages), and HLA-DR (human leukocyte antigen-DR) antigens (activation marker). Immunopositive cells were quantified as cells/mm2. Polymerase chain reaction (PCR) and reverse transcription PCR were performed to screen for herpes virus DNA. Stellate ganglia of all 12 LQTS/CPVT patients revealed mild but distinct inflammatory infiltrates composed of T lymphocytes and macrophages, which were diffusely spread, but also clustered in small foci opposed to ganglion cells, interpreted as T-cell-mediated ganglionitis. Morphometric analysis showed that CD3+ and CD8+ T cells/mm2 were significantly higher in the ganglia of LQTS/CPVT cases than in healthy controls (P=0.0018 and P=0.0009, respectively). Molecular analyses were negative for neurotropic viruses. CONCLUSIONS: T-cell-mediated cytotoxicity toward ganglion cells may boost adrenergic activity as to trigger or enhance electric instability in LQTS/CPVT patients who are already genetically predisposed to arrhythmias.