title: The impact of vitamin D on dendritic cell function in patients with systemic lupus erythematosus.
abstract: BACKGROUND
  Excessive activity of dendritic cells (DCs) is postulated as a central disease mechanism in Systemic Lupus Erythematosus (SLE). Vitamin D is known to reduce responsiveness of healthy donor DCs to the stimulatory effects of Type I IFN. As vitamin D deficiency is reportedly common in SLE, we hypothesized that vitamin D might play a regulatory role in the IFNalpha amplification loop in SLE. Our goals were to investigate the relationship between vitamin D levels and disease activity in SLE patients and to investigate the effects of vitamin D on DC activation and expression of IFNalpha-regulated genes in vitro.
  
  
  RESULTS
  In this study, 25-OH vitamin D (25-D) levels were measured in 198 consecutively recruited SLE patients. Respectively, 29.3% and 11.8% of African American and Hispanic SLE patient had 25-D levels <10 ng/ml. The degree of vitamin D deficiency correlated inversely with disease activity; R = -.234, p = .002. In 19 SLE patients stratified by 25-D levels, there were no differences between circulating DC number and phenotype. Monocyte-derived DCs (MDDCs) of SLE patients were normally responsive to the regulatory effects of vitamin D in vitro as evidenced by decreased activation in response to LPS stimulation in the presence of 1,25-D. Additionally, vitamin D conditioning reduced expression of IFNalpha-regulated genes by healthy donor and SLE MDDCs in response to factors in activating SLE plasma.
  
  
  CONCLUSIONS
  We report on severe 25-D deficiency in a substantial percentage of SLE patients tested and demonstrate an inverse correlation with disease activity. Our results suggest that vitamin D supplementation will contribute to restoring immune homeostasis in SLE patients through its inhibitory effects on DC maturation and activation. We are encouraged to support the importance of adequate vitamin D supplementation and the need for a clinical trial to assess whether vitamin D supplementation affects IFNalpha activity in vivo and, most importantly, improves clinical outcome.
authors.affiliation: Division of Autoimmune and Musculoskeletal Disease, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Zvi
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aranow
authors.forename: Meggan
authors.initials: M
authors.lastname: Mackay
authors.forename: Anfisa
authors.initials: A
authors.lastname: Stanevsky
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: L Manuela
authors.initials: LM
authors.lastname: Marinescu
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Collins
authors.forename: Gary S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.forename: John A
authors.initials: JA
authors.lastname: Hardin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D000941:Antigens / Q000235:genetics; D044466:Asian People / Q000706:statistics & numerical data; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D003598:Cytoskeletal Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000208:ethnology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000097:blood* / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000097:blood* / Q000208:ethnology; D044465:White People / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C065888:IFI44 protein, human; C484290:IFIT1 protein, human; D064547:Myxovirus Resistance Proteins; D016601:RNA-Binding Proteins; D014807:Vitamin D; D019204:GTP-Binding Proteins