Complement Consumption in Systemic Lupus Erythematosus Leads to Decreased Opsonophagocytosis In Vitro.

ABSTRACT

OBJECTIVE: Infections remain a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The high prevalence of infections in SLE is attributed to both the disease and its treatments. The complement system plays an important role in host immune responses against invading microorganisms. We sought to provide the experimental and clinical evidence supporting the hypothesis that low levels of complement factors cause defective complement-mediated opsonization in patients with SLE. METHODS: Staphylococcus aureus was opsonized with sera from healthy individuals (n = 16), SLE patients with normal (n = 5) or low complement (n = 8) levels. Phagocytosis of S. aureus by healthy human neutrophils was analyzed by an imaging flow cytometry-based method. We retrospectively examined the infection incidence in relation to complement levels in a cohort of 165 patients with SLE during a 1.5-year period. The association was analyzed for infection incidence and disease-related variables. RESULTS: Uptake of S. aureus by neutrophils was decreased when S. aureus was opsonized with sera from SLE patients with low complement levels compared to sera from healthy individuals and SLE patients with normal complement. In our SLE cohort, 44% of patients had at least 1 infection during the 1.5 years. No significant association was observed between complement levels and infection risk. Importantly, high-dose glucocorticoids (GC; prednisone ≥ 10 mg/day) were the most important predictive factor for infections in patients with SLE. CONCLUSION: Low complement levels affect bacterial opsonization in SLE blood and lead to downregulated phagocytosis by neutrophils. High-dose GC increase the infection risk in patients with SLE.