Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus
- Lauren L Ritterhouse1,2,
- Sherry R Crowe1,
- Timothy B Niewold3,
- Diane L Kamen4,
- Susan R Macwana1,
- Virginia C Roberts1,
- Amy B Dedeke1,2,
- John B Harley1,5,
- R Hal Scofield1,2,
- Joel M Guthridge1,
- Judith A James1,2
- 1Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
- 2Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
- 3Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA
- 4Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA
- 5Division of Rheumatology, Cincinnati Children's Hospital Medical Center and US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
- Correspondence to Judith A James, Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA; judith-james{at}omrf.org
- Accepted 1 April 2011
- Published Online First 17 May 2011
Abstract
Objectives Vitamin D deficiency is widespread and has been associated with many chronic diseases, including autoimmune disorders. A study was undertaken to explore the impact of low vitamin D levels on autoantibody production in healthy individuals, as well as B cell hyperactivity and interferon α (IFNα) activity in patients with systemic lupus erythematosus (SLE).
Methods Serum samples from 32 European American female patients with SLE and 32 matched controls were tested for 25-hydroxyvitamin D (25(OH)D) levels, lupus-associated autoantibodies and serum IFNα activity. Isolated peripheral blood mononuclear cells were tested for intracellular phospho-ERK 1/2 as a measure of B cell activation status.
Results Vitamin D deficiency (25(OH)D <20 ng/ml) was significantly more frequent among patients with SLE (n=32, 69%) and antinuclear antibody (ANA)-positive controls (n=14, 71%) compared with ANA-negative controls (n=18, 22%) (OR 7.7, 95% CI 2.0 to 29.4, p=0.003 and OR 8.8, 95% CI 1.8 to 43.6, p=0.011, respectively). Patients with high B cell activation had lower mean (SD) 25(OH)D levels than patients with low B cell activation (17.2 (5.1) vs 24.2 (3.9) ng/ml; p=0.009). Patients with vitamin D deficiency also had higher mean (SD) serum IFNα activity than patients without vitamin D deficiency (3.5 (6.6) vs 0.3 (0.3); p=0.02).
Conclusions The observation that ANA-positive healthy controls are significantly more likely to be deficient in vitamin D than ANA-negative healthy controls, together with the finding that vitamin D deficiency is associated with certain immune abnormalities in SLE, suggests that vitamin D plays an important role in autoantibody production and SLE pathogenesis.
Footnotes
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Funding This work was supported by the National Institutes of Health (NIAID: HHSN266200500026C, AR058554, RR015577, AI082714, AI24717, AR24260, AI083194, AR052364 and AR053483), Kirkland Scholar Award Program at The Hospital for Special Surgery in New York City which is funded exclusively by Rheuminations, Inc., a non-profit foundation dedicated to supporting research leading to the treatment and cure of lupus, OMRF J Donald Capra Fellowship Support, US Department of Veteran Affairs and the OMRF Lou C Kerr Chair in Biomedical Research.
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Competing interests JBH has served as a consultant for BioRad and owns stock in IVAX Diagnostics. All other authors have no competing interest.
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Ethics approval This study was conducted with the approval of the Oklahoma Medical Research Foundation (OMRF) and the University of Oklahoma Health Sciences Center.
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Provenance and peer review Not commissioned; externally peer reviewed.








