Effects of BAFF Neutralization on Atherosclerosis Associated With Systemic Lupus Erythematosus

Abstract

Objective Cardiovascular disease (CVD) is the leading cause of death in systemic lupus erythematosus (SLE). B cells play a key role in the pathogenesis of lupus, and anti‐BAFF therapy has been approved for use in SLE. Since mature B cells also promote atherosclerosis, we undertook this study to evaluate, in a mouse model and in SLE patients, whether BAFF neutralization has an atheroprotective effect in SLE. Methods The effect of BAFF on atherosclerosis associated with lupus was investigated in the atherosclerosis/lupus‐prone apolipoprotein E–knockout D227K mouse model and in a cohort of SLE patients. Mice were treated with a blocking anti‐BAFF monoclonal antibody (mAb), while fed a standard chow diet. Carotid plaque and carotid intima‐media thickness were assessed by ultrasound at baseline and during follow‐up in SLE patients who were asymptomatic for CVD. Results Anti‐BAFF mAb in ApoE−/− D227K mice induced B cell depletion, efficiently treated lupus, and improved atherosclerosis lesions (21% decrease; P = 0.007) in mice with low plasma cholesterol levels but worsened the lesions (17% increase; P = 0.06) in mice with high cholesterol levels. The atheroprotective effect of the BAFF–BAFF receptor signaling inhibition on B cells was counterbalanced by the proatherogenic effect of the BAFF–TACI signaling inhibition on macrophages. In SLE patients, blood BAFF levels were associated with subclinical atherosclerosis (r = 0.26, P = 0.03). Anti‐BAFF mAb treatment had a differential effect on the intima‐media thickness progression in SLE patients depending on body mass index. Conclusion Depending on the balance between lipid‐induced and B cell–induced proatherogenic conditions, anti‐BAFF could be detrimental or beneficial, respectively, to atherosclerosis development in SLE.

Osteopontin targeted theranostic nanoprobes for laser-induced synergistic regression of vulnerable atherosclerotic plaques

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Soluble CD163 and incident cardiovascular events in patients with systemic lupus erythematosus: An observational cohort study

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Cardiovascular disease in systemic lupus erythematosus

“…[ 147 , 148 ] Recent data in a mouse model of lupus and atherosclerosis found that BAFF inhibition improved atherosclerosis lesions in mice with low plasma cholesterol levels but worsened the lesions in mice with high cholesterol levels. [ 149 ]…”