title: Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aranow
authors.affiliation: Medical University of South Carolina, Charleston.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.affiliation: University of California, San Francisco.
authors.forename: Maria
authors.initials: M
authors.lastname: Dall'Era
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Massarotti
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Meggan C
authors.initials: MC
authors.lastname: Mackay
authors.affiliation: West Penn Hospital, Pittsburgh, Pennsylvania.
authors.forename: Fotios
authors.initials: F
authors.lastname: Koumpouras
authors.affiliation: University of Rochester, Rochester, New York.
authors.forename: Andreea
authors.initials: A
authors.lastname: Coca
authors.affiliation: University of Alabama at Birmingham.
authors.forename: W Winn
authors.initials: WW
authors.lastname: Chatham
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Megan E B
authors.initials: ME
authors.lastname: Clowse
authors.affiliation: Duke University Medical Center, Durham, North Carolina.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Criscione-Schreiber
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
authors.forename: Sherri
authors.initials: S
authors.lastname: Callahan
authors.affiliation: National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland.
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Goldmuntz
authors.affiliation: Rho Federal Systems, Chapel Hill, North Carolina.
authors.forename: Lynette
authors.initials: L
authors.lastname: Keyes-Elstein
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Michaela
authors.initials: M
authors.lastname: Oswald
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.affiliation: Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D000941:Antigens / Q000097:blood* / Q000235:genetics; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000097:blood* / Q000235:genetics; D004247:DNA / Q000276:immunology; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins / Q000097:blood* / Q000235:genetics; D011446:Prospective Studies; D016601:RNA-Binding Proteins; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C065888:IFI44 protein, human; C484290:IFIT1 protein, human; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D016601:RNA-Binding Proteins; D014807:Vitamin D; D002762:Cholecalciferol; D004247:DNA; C104450:25-hydroxyvitamin D