Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus

• Published in: Annals of the rheumatic diseases Vol. 70; no. 9; pp. 1569 - 1574
• Main Authors: Ritterhouse, Lauren L, Crowe, Sherry R, Niewold, Timothy B, Kamen, Diane L, Macwana, Susan R, Roberts, Virginia C, Dedeke, Amy B, Harley, John B, Scofield, R Hal, Guthridge, Joel M, James, Judith A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.09.2011; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Antibodies, Antinuclear - blood; Autoimmunity - immunology; B-Lymphocytes - immunology; Biological and medical sciences; Case-Control Studies; Dendritic cells; Diabetes; Disease; Diseases of the osteoarticular system; Female; Humans; Inflammatory bowel disease; Interferon-alpha - blood; Lupus; Lupus Erythematosus, Systemic - etiology; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation - immunology; Medical sciences; Pathogenesis; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Studies; Vitamin D; Vitamin D - analogs & derivatives; Vitamin D - blood; Vitamin D Deficiency - complications; Vitamin D Deficiency - immunology; Vitamin deficiency; California; Autoimmunity; Human; Immunopathology; Connective tissue disease; Skin disease; Systemic lupus erythematosus; Systemic disease; Nutrition disorder; Rheumatology; Autoimmune disease; Nutritional status
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard.2010.148494

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.