THU0309 Coronary Heart Disease in Systemic Lupus Erythematosus is Associated with Interferon Regulatory Factor 8 Gene Variants

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A270.2-A270
Author(s):  
D. Leonard ◽  
E. Svenungsson ◽  
J. K. Sandling ◽  
O. Berggren ◽  
A. Jönsen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lupus Erythematosus ◽  
Interferon Regulatory Factor ◽  
Gene Variants ◽  
Regulatory Factor ◽  
Systemic Lupus

scholarly journals Risk Factors for Clinical Coronary Heart Disease in Systemic Lupus Erythematosus: The Lupus and Atherosclerosis Evaluation of Risk (LASER) Study

2009 ◽  
Vol 37 (2) ◽  
pp. 322-329 ◽  
Author(s):  
SAHENA HAQUE ◽  
CAROLINE GORDON ◽  
DAVID ISENBERG ◽  
ANISUR RAHMAN ◽  
PETER LANYON ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lupus Erythematosus ◽  
Clinical Setting ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Chd Risk ◽  
Control Disease

Objective. Accelerated atherosclerosis and premature coronary heart disease (CHD) are recognized complications of systemic lupus erythematosus (SLE), but the exact etiology remains unclear and is likely to be multifactorial. We hypothesized that SLE patients with CHD have increased exposure to traditional risk factors as well as differing disease phenotype and therapy-related factors compared to SLE patients free of CHD. Our aim was to examine risk factors for development of clinical CHD in SLE in the clinical setting.Methods. In a UK-wide multicenter retrospective case-control study we recruited 53 SLE patients with verified clinical CHD (myocardial infarction or angina pectoris) and 96 SLE patients without clinical CHD. Controls were recruited from the same center as the case and matched by disease duration. Charts were reviewed up to time of event for cases, or the same “dummy-date” in controls.Results. SLE patients with clinical CHD were older at the time of event [mean (SD) 53 (10) vs 42 (10) yrs; p < 0.001], more likely to be male [11 (20%) vs 3 (7%); p < 0.001], and had more exposure to all classic CHD risk factors compared to SLE patients without clinical CHD. They were also more likely to have been treated with corticosteroids (OR 2.46; 95% CI 1.03, 5.88) and azathioprine (OR 2.33; 95% CI 1.16, 4.67) and to have evidence of damage on the pre-event SLICC damage index (SDI) (OR 2.20; 95% CI 1.09, 4.44). There was no difference between groups with regard to clinical organ involvement or autoantibody profile.Conclusion. Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

Longitudinal Evolution of Risk of Coronary Heart Disease in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (5) ◽  
pp. 968-973 ◽  
Author(s):  
IGOR KARP ◽  
MICHAL ABRAHAMOWICZ ◽  
PAUL R. FORTIN ◽  
LOUISE PILOTE ◽  
CAROLYN NEVILLE ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Blood Glucose ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Chd Risk ◽  
Over Time

Objective.To produce evidence on the longitudinal evolution of risk factors for coronary heart disease (CHD) in patients with systemic lupus erythematosus (SLE).Methods.Based on data for 115 patients from the Montreal General Hospital Lupus Clinic (1971–2003) and for 4367 control subjects from the Framingham Offspring Study (1971–1994), we investigated the temporal evolution of total serum cholesterol, systolic blood pressure (SBP), body mass index (BMI), blood glucose, and estimated risk for CHD (reflecting the balance of changes in different risk factors). In analyses limited to patients with SLE, we assessed the effect of SLE duration on each risk factor, adjusting for age, calendar time, sex, baseline level of the risk factor, and medication use. Next, we assessed how the adjusted difference in the values of the risk factors between SLE and controls changes over time.Results.Among patients with SLE, longer disease duration was independently associated with higher SBP and blood glucose levels. Compared with controls, these patients appeared to have accelerated rates of increase in total cholesterol, blood glucose, and overall estimated CHD risk. The rate of increase in BMI was lower in patients with SLE than in controls.Conclusion.Elevated CHD risk in patients with SLE appears to be at least partially mediated by accelerated increases in some CHD risk factors, longitudinal trajectories of which increasingly diverge over time from those of population controls.

scholarly journals Interferon Regulatory Factor 5 in the Pathogenesis of Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Candace M. Cham ◽  
Kichul Ko ◽  
Timothy B. Niewold
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Interferon Regulatory Factor ◽  
Immune Defense ◽  
Toll Like Receptors ◽  
Regulatory Factor ◽  
Systemic Lupus ◽  
Interferon Regulatory Factor 5

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple genetic risk factors, high levels of interferon alpha (IFN-α), and the production of autoantibodies against components of the cell nucleus. Interferon regulatory factor 5 (IRF5) is a transcription factor which induces the transcription of IFN-αand other cytokines, and genetic variants of IRF5 have been strongly linked to SLE pathogenesis. IRF5 functions downstream of Toll-like receptors and other microbial pattern-recognition receptors, and immune complexes made up of SLE-associated autoantibodies seem to function as a chronic endogenous stimulus to this pathway. In this paper, we discuss the physiologic role of IRF5 in immune defense and the ways in whichIRF5variants may contribute to the pathogenesis of human SLE. Recent data regarding the role ofIRF5in both serologic autoimmunity and the overproduction of IFN-αin human SLE are summarized. These data support a model in which SLE-risk variants of IRF5 participate in a “feed-forward” mechanism, predisposing to SLE-associated autoantibody formation, and subsequently facilitating IFN-αproduction downstream of Toll-like receptors stimulated by immune complexes composed of these autoantibodies.

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