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;
- Accepted 1 April 2011
- Published Online First 17 May 2011
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.
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.
Competing interests JBH has served as a consultant for BioRad and owns stock in IVAX Diagnostics. All other authors have no competing interest.
Ethics approval This study was conducted with the approval of the Oklahoma Medical Research Foundation (OMRF) and the University of Oklahoma Health Sciences Center.
Provenance and peer review Not commissioned; externally peer reviewed.