Anti-Ro/SSA-associated corrected QT interval prolongation in adults: the role of antibody level and specificity

Arthritis Care Res (Hoboken). 2011 Oct;63(10):1463-70. doi: 10.1002/acr.20540.

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.

Conclusion: 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.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood*
  • Antibody Specificity*
  • Arrhythmias, Cardiac / diagnosis
  • Arrhythmias, Cardiac / immunology*
  • Arrhythmias, Cardiac / physiopathology
  • Autoimmunity
  • Biomarkers / blood
  • Blotting, Western
  • Cross Reactions
  • Electrocardiography
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heart Conduction System / immunology*
  • Heart Conduction System / physiopathology
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Risk Assessment
  • Risk Factors
  • Up-Regulation

Substances

  • Antibodies, Antinuclear
  • Biomarkers
  • SS-A antibodies