Date: Monday, October 22, 2018
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Long QT syndrome (LQTS) is an abnormal QT corrected (QTc) interval prolongation, strongly associated with increased risk of sudden death. Studies have associated LQTS with autoimmune conditions, and evidence points towards a link between inflammation and LQTS. We already demonstrated that LQTS occurs in SLE patients positive to anti-Ro/SSA antibodies, and interference with ventricular repolarization is linearly associated with levels of anti-Ro52/TRIM21 antibodies. However, critical cytokine pathways facilitating the development of LQTS in SLE are still unknown. This study was conducted to evaluate the cytokine milieu in SLE patients with LQTS.
Methods: Consecutive patients fulfilling the 1997 ACR criteria for SLE were included. Patients with a history of ischemic heart disease or implantable pacemakers, and those taking drugs potentially affecting QT interval (except for antimalarials) were excluded. Patients underwent a resting 12-lead ECG recording to measure QTc interval (Bazzet’s formula). A QTc interval duration >460 msec in women and >440 msec in men was set to define LQTS. Serum cytokine and chemokine levels were measured by multiplex bead array technology.
Results: Sixty-six patients with a mean age of 39±13 years (57 female gender) were included. A LQTS 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 in both groups, except for a lesser use of antimalarials in patients with LQTS. Disease activity was similar between groups. Anti-Ro/SSA (75±66 U/mL versus 29±44 U/mL; P=0.005) and anti-Ro52/TRIM21 (50±55 U/mL versus 14±30 U/mL; P=0.01) antibody levels were higher in patients with LQTS.
Regarding serum cytokines, levels of type I IFN-induced chemokines IP-10 (425±258 pg/mL versus 275±267 pg/mL; P=0.021) and IL-8 (58±52 pg/mL versus 29±24 pg/mL; P=0.039) were significantly higher in patients with LQTS. Notably, anti-Ro/SSA antibody levels were linearly associated with IP-10 (r=0.41, 95%CI 0.18–0.60; P=0.0002) and IL-8 (r=0.31, 0.06–0.52; P=0.005) levels. In addition, anti-Ro52/TRIM21 antibody levels also were linearly correlated with IP-10 (r=0.39, 0.16–0.58; P=0.0005) and IL-8 (r=0.23, -0.02–0.45; P=0.03) levels. Other type I IFN-induced chemokines (MCP-1 and RANTES) were similar between groups.
No differences in the cytokine circuits characterizing Th1 (IFN-g, IL-2, IL-12, IL-27), Th2 (IL-4, IL-5, IL-13, IL-6), Th17 (IL-17, IL-21, IL-22, IL-6, GM-CSF, IL-23), Th9 (IL-9, IL-4, IL-21, IL-6), Th22 (IL-22, TNF, IL-6, IL-10), Tr1 (IL-10, IFN-g, IL-27) were found. Additionally, no differences were found in other chemokines (MIP-1α, SDF-1, IL-18, GRO-α, Eotaxin, MIP-1β) characteristic of innate immunity.
Conclusion: Our results reinforce the existence of a specific LQTS mediated by anti-Ro/SSA autoantibodies, especially those specifically directed against the antigen Ro52/TRIM21. The interference in ventricular repolarization seems to be driven by proteins from the IFN gene signature, which is in line with the notion that Ro52/TRIM21 antigens are an element of response to type I IFN.
To cite this abstract in AMA style:Perez-Garcia LF, Estevez-Garcia IO, Marquez-Velasco R, Iturralde P, Silveira LH, Amezcua-Guerra LM. Type I Interferon-Induced Proteins May Facilitate the Occurrence of Long QT Syndrome (LQTS) in Parallel with Anti-Ro/SSA and Anti-Ro52/TRIM21 Antibody Levels in Patients with Systemic Lupus Erythematous (SLE): A Bench to Bedside Approach [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/type-i-interferon-induced-proteins-may-facilitate-the-occurrence-of-long-qt-syndrome-lqts-in-parallel-with-anti-ro-ssa-and-anti-ro52-trim21-antibody-levels-in-patients-with-systemic-lupus-erythemato/. Accessed April 16, 2021.
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