Elevated serum complement levels and higher gene copy number of complement C4B are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE)
| Autor: | Haikady N. Nagaraja, Yee Ling Wu, Nora G. Singer, Susan D. Thompson, Deborah M. Levy, Stacy P. Ardoin, Hermine I. Brunner, Bi Zhou, Chack-Yung Yu, Evan Mulvihill, Laura E. Schanberg, Emily King, Gakit Richard Yu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
030203 arthritis & rheumatology
0301 basic medicine medicine.medical_specialty Lupus erythematosus business.industry Atorvastatin Immunology C4A General Medicine Disease Placebo medicine.disease Gastroenterology 3. Good health Clinical trial 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Blood pressure Intima-media thickness Internal medicine medicine business medicine.drug |
| Zdroj: | Lupus Science & Medicine. 6:e000333 |
| ISSN: | 2053-8790 |
| DOI: | 10.1136/lupus-2019-000333 |
| Popis: | ObjectiveSystemic 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 complement and CVD in cSLE.MethodsGene copy numbers (GCNs) for total C4, C4A and C4B were measured by TaqMan-based real-time PCR and Southern blotting, and analysed with laboratory and clinical parameters through Student’s t-test and χ2 analyses. Effects of total C4, C4A and C4B GCNs on the response to placebo or atorvastatin treatment and progression of CIMT were examined by regression analyses.ResultsAt baseline, C4 protein levels strongly correlated with GCNs of total C4 (p=1.8×10−6). Each copy of C4 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=5.0×10−25; C3: P=5.84×10−20). Individuals with ≥2 C4B 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 C4B deficiency. At the study end, subjects with ≥2 C4B and atorvastatin treatment had significantly slower increase in CIMT compared with those treated with placebo (p=0.018).ConclusionscSLE with hypertension had elevated serum levels of C4 and C3 and higher GCN of C4B; cSLE with ≥2 C4B genes would benefit from statins therapy to prevent atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|