Abstract
IntroductionIn a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia.MethodsA protein array was utilized to measure ferritin expression in the urine and serum of SLE patients and healthy controls. To confirm these results as well as the role of the iron transfer pathway in SLE, ELISAs were performed to measure ferritin and transferrin levels in inactive or active SLE patients and healthy controls. The relationship between ferritin/transferrin levels and inflammatory markers and anemia was next analyzed.ResultsProtein array results showed elevated ferritin levels in the serum and urine of lupus patients as compared to controls, which were further validated by ELISA. Increased ferritin levels correlated with measures of disease activity and anemia as well as inflammatory cytokine titers. Though active SLE patients had elevated urine transferrin, serum transferrin was reduced.ConclusionUrine ferritin and transferrin levels are elevated significantly in SLE patients and correlate with disease activity, bolstering previous reports. Most importantly, these changes correlated with the inflammatory state of the patients and anemia of chronic disease. Taken together, altered iron handling, inflammation and anemia of chronic disease constitute an ominous triad in SLE.
Highlights
In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased
While the increased ferritin levels in SLE patient sera (N = 5) measured by this array were not statistically significant (P = 0.155), urine ferritin levels were significantly increased (P = 0.020) in lupus nephritis (LN) patients compared to healthy controls
To validate the array results, serum samples from healthy, inactive SLE and active SLE patients were examined for ferritin levels using ELISA
Summary
In a recent screening to detect biomarkers in systemic lupus erythematosus (SLE), expression of the iron storage protein, ferritin, was increased. Given that proteins that regulate the storage, transfer and release of iron play an important role in inflammation, this study aims to determine the serum and urine levels of ferritin and of the iron transfer protein, transferrin, in lupus patients and to correlate these levels with disease activity, inflammatory cytokine levels and markers of anemia. In an effort to identify novel markers of disease activity in systemic lupus erythematosus (SLE), we recently compared serum and urine samples from SLE patients against that of healthy controls, using glass-slide arraybased screens. High concentrations of serum ferritin levels have been reported in patients with active SLE as compared to inactive SLE [6,7,8]. Elevated levels of urinary ferritin have been reported in lupus nephritis (LN) patients [9]
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