SummaryErythrocyte complement receptor type one (E-CR1) is thought to protect against immune complex (IC) disease through interactions that lead to E-CR1 consumption, and low E-CR1 levels are characteristic of systemic lupus erythematosus (SLE). The purpose of this study was to test the hypothesis that E-CR1 consumption can predict or mark SLE flare. Recurrently active SLE patients [ n = = = = 43; 28 with past or present major renal manifestations (SLER) and 15 without (SLENR)], were evaluated every 2 months by detailed protocol testing (mean follow-up 22 months), including direct measurements of E-CR1 levels using a radioimmunoassay. In all patients, detectable E-CR1 levels fluctuated widely through acute periods of consumption and regeneration, preventing the use of any single value as a baseline. However, when individual chronic baseline values were used, determined as the mean of all E-CR1 values 4 months or more from a flare, a clear trend was observed. In 16 of 16 instances of non-renal flare in SLER patients, E-CR1 levels decreased at flare (mean decrease 34%, P < 0·0001). In contrast, no consistent difference was observed for flare in SLENR patients or for renal flare in SLER patients. Changes in E-CR1 levels did not correlate with plasma CR1 levels. In conclusion, single occurrences of E-CR1 consumption did not generally predict or mark SLE flare. However, compared to the average E-CR1 levels measured during no-flare intervals, E-CR1 consumption in SLER patients at flare was strongly associated with freedom from signs of renal involvement. We postulate that E-CR1 consumption reflects E-CR1 function that includes protecting against SLE nephritis.

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Interleukin 1β (IL-1β) is a proinflammatory cytokine that has been implicated in a number of rheumatologic and inflammatory conditions. The production and secretion of IL-1β from inflammatory cells is a tightly regulated process that has been extensively described and studied. In recent years, IL-1β has been associated with several steps in the development of atherosclerotic plaques, as well as other cardiovascular disease modifiers, such as cigarette smoking and type II diabetes mellitus. More recently, IL-1β has become the target of therapy in refractory rheumatologic conditions and is under investigation as a potential target of therapy in cardiovascular disease. The Canakinumab Anti-inflammatory Thrombosis Outcomes Study is currently underway and strives to use canakinumab, a monoclonal antibody directed against IL-1β, to evaluate the inflammatory hypothesis of cardiovascular disease. If the trial meets its primary end points (eg, significant reductions in nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), the Canakinumab Anti-inflammatory Thrombosis Outcomes Study will confirm the critical role of IL-1β-mediated inflammation in the development of cardiovascular disease and will introduce cytokine-directed therapy as a potential avenue for the treatment of atherosclerotic disease.

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