Background/Purpose: Long QT syndrome (LQTS) is characterized by an abnormal QT corrected (QTc) interval prolongation that is associated with increased risk of sudden death. Studies have associated LQTS with several rheumatic conditions, and evidence points towards a link between the degree of systemic inflammation and the duration of QTc interval. Moreover, recent evidence suggests that anti-Ro antibodies may play a role in the QTc prolongation by mechanisms not fully understood, thus constituting a novel autoimmune-mediated LQTS. This study was aimed to assess whether QTc interval prolongation is associated with the presence of anti-Ro antibodies in SLE, particularly with reactivities against Ro52/TRIM21 antigens.

Methods: Consecutive patients fulfilling the 1997 ACR criteria for SLE were included. Patients with history of ischemic heart disease, with implantable pacemakers, and those taking drugs that potentially could affect QT interval (except for antimalarials) were excluded. Patients underwent a resting 12-lead electrocardiogram recording to measure QT interval corrected by BazzetÕs formula. A QTc interval duration greater than 460 msec in women and 440 msec in men was set to be abnormal. Serum anti-Ro and anti-Ro52/TRIM21 antibody levels were measured by ELISA. Data were expressed as frequencies and means (± standard deviation), and differences were tested by YatesÕ continuity corrected chi square or Mann-Whitney tests, while linear regressions were performed to assess linearity between autoantibody levels and QTc duration. The GraphPad Prism 4.02 software was used for calculations.

Results: Sixty-six patients with mean age of 39±13 years (57 female gender) were included. A QTc prolongation was found in 10 patients (15%), with mean QTc interval of 470±18 msec as compared to 414±23 msec in those with no LQTS. Main clinical and demographic characteristics were similar for both groups, except for a lesser use of antimalarials and higher serum creatinine levels in patients with LQTS. Disease activity was similar between groups.Anti-Ro antibody levels were significantly higher in patients with prolonged QT interval (75±66 U/mL versus 29±44 U/mL; P=0.005); similarly, anti-Ro52/TRIM21 levels were higher in those with LQTS (50±55 U/mL versus 14±30 U/mL; P=0.01). Notably, a linear association (see the Figure) between the QTc intervals and levels of anti-Ro antibodies (r²=0.073; P=0.02) and anti-Ro52/TRIM21antibodies (r²=0.078; P=0.02) was observed.

Conclusion: Our results strengthen the hypothesis that a specific autoantibody-mediated LQTS occur in SLE patients positive to anti-Ro antibodies. This interference in the ventricular repolarization appears to be associated with increased levels of antibodies against Ro52/TRIM21 antigens, and supports the realization of an electrocardiogram as part of the routinely evaluation in SLE patient with circulating anti-Ro antibodies.