title: Reversing bacteria-induced vitamin D receptor dysfunction is key to autoimmune disease.
abstract: Vitamin D research is discussed in light of the hypothesis that the lower average levels of vitamin D frequently observed in autoimmune disease are not a sign of deficiency. Instead, it is proposed that the lower levels result from chronic infection with intracellular bacteria that dysregulate vitamin D metabolism by causing vitamin D receptor (VDR) dysfunction within phagocytes. The VDR dysfunction causes a decline in innate immune function that causes susceptibility to additional infections that contribute to disease progression. Evidence has been accumulating that indicates that a number of autoimmune diseases can be reversed by gradually restoring VDR function with the VDR agonist olmesartan and subinhibitory dosages of certain bacteriostatic antibiotics. Diseases showing favorable responses to treatment so far include systemic lupus erythematosis, rheumatoid arthritis, scleroderma, sarcoidosis, Sjogren's syndrome, autoimmune thyroid disease, psoriasis, ankylosing spondylitis, Reiter's syndrome, type I and II diabetes mellitus, and uveitis. Disease reversal using this approach requires limitation of vitamin D in order to avoid contributing to dysfunction of nuclear receptors and subsequent negative consequences for immune and endocrine function. Immunopathological reactions accompanying bacterial cell death require a gradual elimination of pathogens over several years. Practical and theoretical implications are discussed, along with the compatibility of this model with current research.
authors.affiliation: Autoimmunity Research Foundation, Thousand Oaks, California 91360, USA. jcw@autoimmunityresearch.org
authors.forename: Joyce C
authors.initials: JC
authors.lastname: Waterhouse
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Perez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Albert
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016918:Arthritis, Reactive / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000503:physiopathology*; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008911:Minocycline / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000502:physiology*; D012507:Sarcoidosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000627:therapeutic use; D013959:Thyroid Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D014605:Uveitis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D018167:Receptors, Calcitriol; D013777:Tetrazoles; C437965:olmesartan; D002117:Calcitriol; D008911:Minocycline; D002112:Calcifediol