作者：Aranow C 等 翻译：张警丰
发布者：武东 审校者：金银姬
1
目的
在系统性红斑狼疮（SLE）中，维生素D有调节免疫反应和阻止干扰素应答的作用。本研究的目的是分析补充维生素D对SLE患者干扰素应答的影响。
2
方法
共纳入57例SLE患者，为稳定，非活动患者，血清25[OH]D水平≤20 ng/ml，血清抗ds-DNA水平升高，具有IFN标记（定义为能够检测到3个IFN反应基因），随机分至2000IU维生素D3组与4000IU维生素D3组，本研究为期12周，为双盲、空白对照试验。IFN应答反应定义为3个基因中有1个表达下降50%或3个基因中有2个表达下降25%。同时评估疾病活动度，副反应和内分泌作用。
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结果
三组（空白对照，低剂量维生素D3或高剂量维生素D3）在基线时的特征无差异。空白对照无一例出现25(OH)D水平升高（≥30 ng/ml），33例摄入维生素D3的患者有16例25(OH)D水平升高达标。在治疗组间具有干扰素应答反应的患者比例无差异。此外，在仍有维生素D缺乏的患者和维生素D水平已经补足的患者间，具有IFN应答反应的患者比例无差异。对40例患者的亚组进行分子微阵列分析发现，在任一治疗组中自基线起各种分子（包括干扰素诱导分子）均无变化，且在维生素D已经补足的患者和仍有维生素D 缺乏的患者中表达无显著差异。维生素D 的耐受性好，无不良事件发生。
4
结论
每日补充维生素D3 4000IU是安全的，且耐受性好，但不能减少维生素D缺乏SLE患者的IFN应答。可能需要维持高水平25(OH)D更长的时间方可影响免疫反应。
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附原文
Abstract：OBJECTIVE: Vitamin 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.METHODS: SLE 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 D3 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.RESULTS: Baseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or
high-dose vitamin D3 ) 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 D3 . 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 D3 was well tolerated, and there were no safety concerns.CONCLUSION: Vitamin D3 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.
6
引自
Aranow C, Kamen DL, Dall'Era M,et al. Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2015 Jul;67(7):1848-57.
