title: T-cell-mediated inflammatory activity in the stellate ganglia of patients with ion-channel disease and severe ventricular arrhythmias.
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.
  
  
  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.
authors.affiliation: Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rizzo
authors.forename: Cristina
authors.initials: C
authors.lastname: Basso
authors.forename: Dirk
authors.initials: D
authors.lastname: Troost
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.forename: Antoine H G
authors.initials: AH
authors.lastname: Driessen
authors.forename: Gaetano
authors.initials: G
authors.lastname: Thiene
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Allard C
authors.initials: AC
authors.lastname: van der Wal
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D007473:Ion Channels / Q000378:metabolism*; D008133:Long QT Syndrome / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013233:Stellate Ganglion / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D017180:Tachycardia, Ventricular / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D007473:Ion Channels
keywords: inflammation; long QT syndrome; pathology; polymorphic catecholaminergic ventricular tachycardia; sympathetic nervous system