Elevated serum complement levels and higher gene copy number of complement are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE). Journal Article

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Authors: Mulvihill, E; Ardoin, S; Thompson, SD; Zhou, B; Yu, GR; King, E; Singer, N; Levy, DM; Brunner, H; Wu, YL; Nagaraja, HN; Schanberg, LE; Yu, CY
Article Title: Elevated serum complement levels and higher gene copy number of complement are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE).
Abstract: Objective: Systemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between and CVD in cSLE. Methods: Gene copy numbers (GCNs) for total , and were measured by TaqMan-based real-time PCR and Southern blotting, and analysed with laboratory and clinical parameters through Student's t-test and ? analyses. Effects of total , and GCNs on the response to placebo or atorvastatin treatment and progression of CIMT were examined by regression analyses. Results: At baseline, C4 protein levels strongly correlated with GCNs of total (p=1.8×10). Each copy of gene increased mean serum C4 by 3.28?mg/dL. Compared with those without hypertension (N=142), individuals with hypertension demonstrated significantly elevated serum levels for C4 and C3 at baseline and serially (C4: P=5.0×10; C3: P=5.84×10). Individuals with =2 genes had 2.5 times the odds of having hypertension (p=0.016) and higher diastolic blood pressure (p=0.015) compared with those with deficiency. At the study end, subjects with =2 and atorvastatin treatment had significantly slower increase in CIMT compared with those treated with placebo (p=0.018). Conclusions: cSLE with hypertension had elevated serum levels of C4 and C3 and higher GCN of ; cSLE with =2 genes would benefit from statins therapy to prevent atherosclerosis.
Journal Title: LUPUS SCIENCE MEDICINE
Publisher: Unknown  
Date Published: 2019