Smoking associates with increased BAFF and decreased interferon-γ levels in patients with systemic lupus erythematosus

OBJECTIVE: In SLE, smoking increases the burden of cutaneous disease and organ damage, and leads to premature mortality. However, the effect of smoking on disease manifestations and cytokine levels of patients with SLE is unclear. This study compared characteristics of patients with SLE across smoking status, and determined the association of smoking with serum cytokine levels. METHOD: A cross-sectional study of patients with SLE (n=99) during a research visit in which smoking status was ascertained. Smoking status was compared across classification criteria (American College of Rheumatology Classification Criteria for SLE (ACR97)), disease activity (SLE Disease Activity Index), autoantibody levels, accrued damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index), and circulating concentrations of serum interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-10, IL-12, IL-17, B cell-activating factor (BAFF), tumour necrosis factor-alpha, transforming growth factor beta 1 (TGF-β1), macrophage inflammatory protein 1 alpha (MIP-1α), MIP-1β and monocyte chemoattractant protein 1. Linear regression models determined the association between smoking and cytokine levels, adjusting for age and sex, clinical characteristics (model 1), and anti-inflammatory (IL-4, IL-10 and TGF- β1) and regulatory (IL-1β) cytokines (model 2). RESULTS: Among patients with SLE (97.9% ANA+; mean 48.48 years old; 86.9% female; mean 10 years of disease duration), 35.4% (n=35 of 99) were smoking (an average of 7 cigarettes/day for 24 years). Smokers had increased odds of prevalent ACR97 malar rash (OR 3.40, 95% CI 1.23 to 9.34) and mucosal ulcers (OR 3.31, 95% CI 1.36 to 8.05). Smokers had more arthritis (OR 3.19, 95% CI 1.19 to 8.60), migraine (OR 2.82, 95% CI 1.07 to 7.44), Raynaud’s phenomenon (OR 5.15, 95% CI 1.95 to 13.56) and increased non-steroidal anti-inflammatory drug use (OR 6.88, 95% CI 1.99 to 23.72). Smoking associated with 27% increased BAFF levels (95% CI 6% to 48%) and 42% decreased IFN-γ levels (95% CI −79% to −5%) in model 2. CONCLUSION: In patients with SLE, smoking independently associated with increased BAFF and decreased IFN-γ levels, and an increased frequency of arthritis, migraine and Raynaud’s phenomenon. Smoking cessation is advisable to reduce systemic inflammation, reduce disease activity and improve host defence.