Background/Purpose: Although our current serologic measures of disease activity are useful for predicting flare in some patients, other patients experience disease flare in the absence of fluctuations in complement or antibody titers.  We previously reported that novel inflammatory biomarkers of oxidative stress and endothelial activation, including pro-inflammatory HDL (piHDL), elevated leptin, and soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), independently confer increased risk for carotid artery plaque (ATH).  We hypothesized that biomarkers of ATH are reflective of alternate pathways driving inflammation and disease activity in SLE, and will also be associated with increased non-ATH disease flares.

Methods: We retrospectively calculated longitudinal disease activity and flare measurements for 204 SLE women from our “Biomarkers of Atherosclerosis in SLE” cohort. SELENA-SLEDAI disease activity measures were calculated for each patient visit in the 12 month period following their baseline ATH biomarker assessment.  Mild/moderate and severe flares were categorized at each visit using the SELENA flare tool. Antioxidant function of HDL was measured as the change in fluorescence intensity caused by oxidation of DCFH by LDL in the presence or absence of test HDL. Plasma leptin, sTWEAK, and Lp(a) were measured in the baseline blood samples using ELISA (R&D Biosystems). Homocysteine was measured in the UCLA clinical labs by Fluorescence Polarization Immunoassay.

Results: 57.4% of SLE subjects experienced a mild to moderate flare and 22.5% experienced a severe flare in the 12 months following study entry.  In univariate analysis, high sTWEAK and Lp(a) were positively associated and C3 levels were inversely associated with mild to moderate SLE flares.  High leptin and high homocysteine were positively associated with severe SLE flares. In multivariate analysis controlling for lupus medications and other potential confounders, high levels of sTWEAK were associated with 2.3 fold increased odds ratio (OR) for mild to moderate disease flare (p=0.02), and high leptin (OR 5.4, p=0.04), homocysteine (OR 5.8, p=0.02), and baseline prednisone dose (OR 1.1 , p<0.001) were associated with severe flare (TWEAK trended towards association, OR 2.3, p=0.08).  When we substituted our combined ATH biomarkervariable for individual biomarkers, patients with baseline High risk scores had 6.7 fold increased odds for experiencing a severe flare in the subsequent year, and a shorter time to severe flare (Hazard ratio for high PREDICTS score 3.1, p=0.01).

Conclusion: In conclusion, many of our biomarkers of interest for the progression of ATH in SLE may also have implications for overall progression of disease flares.  A panel of atherosclerosis biomarkers may help identify SLE patients at risk for both cardiovascular and lupus disease related flares.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/inflammatory-biomarkers-of-atherosclerosis-and-oxidative-stress-are-associated-with-disease-flare-in-sle/