Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus.

ObjectiveVitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE. MethodsSLE patients (n=57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level 20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D-3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed. ResultsBaseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D-3, or high-dose vitamin D-3) were similar. Repletion of 25(OH)D (i.e., levels 30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D-3. The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n=40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D-3 was well tolerated, and there were no safety concerns. ConclusionVitamin D-3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes.