title: Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity.
abstract: OBJECTIVE
  Recent evidence suggests that anti-Ro/SSA antibodies, strongly associated with the development of congenital heart block, may also be arrhythmogenic for the adult heart. In fact, anti-Ro/SSA-positive patients with connective tissue disease (CTD) frequently display corrected QT (QTc) prolongation associated with an increase in ventricular arrhythmias. However, QTc prolongation prevalence markedly differs throughout the studies (10-60%), but the reason why is not yet clear. The aim of this study was to evaluate whether anti-Ro/SSA-associated QTc prolongation in adult patients with CTD is related to antibody level and specificity.
  
  
  METHODS
  Forty-nine adult patients with CTD underwent a resting 12-lead electrocardiogram recording to measure QTc interval, and a venous withdrawal to determine anti-Ro/SSA antibody level and specificity (anti-Ro/SSA 52 kd and anti-Ro/SSA 60 kd) by immunoenzymatic methods and Western blotting.
  
  
  RESULTS
  In our population, a direct correlation was demonstrated between anti-Ro/SSA 52-kd level and QTc duration (r = 0.38, P = 0.007), patients with a prolonged QTc had higher levels of anti-Ro/SSA 52 kd with respect to those with a normal QTc (P = 0.003), and patients with a moderate to high level (≥50 units/ml) of anti-Ro/SSA 52 kd showed a longer QTc interval (P = 0.008) and a higher QTc prolongation prevalence (P = 0.008) than those with a low positive/negative level (<50 units/ml). On the contrary, no association was found between QTc and anti-Ro/SSA 60-kd level.
  
  
  CONCLUSIONS
  In anti-Ro/SSA-positive adult patients with CTD, the occurrence of QTc prolongation seems strictly dependent on the anti-Ro/SSA 52-kd level. This finding, possibly explaining the different QTc prolongation prevalence reported, strengthens the hypothesis that an extremely specific autoimmune cross-reaction is responsible for the anti-Ro/SSA-dependent interference on ventricular repolarization.
authors: Department of Clinical Medicine and Immunological Sciences, Division of Clinical Immunology, University of Siena, Siena, Italy. lazzerini7@unisi.it
authors: Pietro Enea
authors: PE
authors: Lazzerini
authors: Pier Leopoldo
authors: PL
authors: Capecchi
authors: Maurizio
authors: M
authors: Acampa
authors: Gabriella
authors: G
authors: Morozzi
authors: Francesca
authors: F
authors: Bellisai
authors: Maria Romana
authors: MR
authors: Bacarelli
authors: Saverio
authors: S
authors: Dragoni
authors: Irene
authors: I
authors: Fineschi
authors: Antonella
authors: A
authors: Simpatico
authors: Mauro
authors: M
authors: Galeazzi
authors: Franco
authors: F
authors: Laghi-Pasini
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D000918:Antibody Specificity; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D015551:Autoimmunity; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D003429:Cross Reactions; D004562:Electrocardiography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006329:Heart Conduction System / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D000974:Antibodies, Antinuclear; D015415:Biomarkers; C035356:SS-A antibodies