Autoimmunity and vitamin D – review Jan 2013

The Implication of Vitamin D and Autoimmunity: a Comprehensive Review.

Clin Rev Allergy Immunol. 2013 Jan 29.
Yang CY, Leung PS, Adamopoulos IE, Gershwin ME.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA.

Historically, vitamin D has been associated with the regulation of bone metabolism. However, increasing evidence demonstrates a strong association between vitamin D signaling and many biological processes that regulate immune responses. The discovery of the vitamin D receptor in multiple immune cell lineages, such as monocytes, dendritic cells, and activated T cells credits vitamin D with a novel role in modulating immunological functions and its subsequent role in the development or prevention of autoimmune diseases. In this review we, discuss five major areas in vitamin D biology of high immunological significance:

• (1) the metabolism of vitamin D;
• (2) the significance of vitamin D receptor polymorphisms in autoimmune diseases, such as **multiple sclerosis,
  • type 1 diabetes mellitus, and
  • systemic lupus erythematosus;
• (3) vitamin D receptor transcriptional regulation of immune cell lineages, including Th1, Th17, Th2, regulatory T, and natural killer T cells;
• (4) the prevalence of vitamin D insufficiency/deficiency in patients with
  • multiple sclerosis,
  • type 1 diabetes mellitus, and
  • systemic lupus erythematosus; and finally,
• (5) the therapeutic effects of vitamin D supplementation on disease severity and progression.

PMID: 23359064

2 Charts

---

Following tables clipped from the PDF:

Take-Home Messages

1. Vitamin D can be spontaneously synthesized from cutaneous cholesterol upon UVB exposure and has pleiotropic effects on the immune system.
2. Vitamin D, after metabolized into a biologically active form, 1,25(OH)2D, and bound to VDR/RXR, can initiate gene transcription and exert its immunomodulatory effects.
3. Both environmental trigger (insufficient sunshine expo-sure) and genetic factor (VDR polymorphism) could contribute a poor vitamin D status.
4. Vitamin D deficiency (low serum levels of 25(OH)D) is prevalent in multiple autoimmune diseases, e.g. MS,TIDM, and SLE.
5. Because the vitamin D status is highly associated with the risk of autoimmunity, vitamin D has been implicated in prevention and protection from autoimmune diseases.

---

References

Note: CrossRef links actually work

• Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87:1080S–1086S
• Agmon-Levin N, Kivity S, Tzioufas AG et al (2012) Low levels of vitamin-D are associated with neuropathy and lymphoma among patients with Sjogren’s syndrome. J Autoimmun 39:234–239 CrossRef
• Giovannucci E, Liu Y, Rimm EB et al (2006) Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 98:451–459 CrossRef
• Giovannucci E (2009) Vitamin D and cancer incidence in the Harvard cohorts. Ann Epidemiol 19:84–88 CrossRef
• Twig G, Shina A, Amital H, Shoenfeld Y (2012) Pathogenesis of infertility and recurrent pregnancy loss in thyroid autoimmunity. J Autoimmun 38:J275–J281 CrossRef
• Anderson JL, May HT, Horne BD et al (2010) Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 106:963–968 CrossRef
• Sood A, Arora R (2010) Vitamin D deficiency and its correlations with increased cardiovascular incidences. Am J Ther 17:e105–e109
• Qazi RA, Martin KJ (2012) Vitamin D in kidney disease: pathophysiology and the utility of treatment. Rheum Dis Clin N Am 38:115–123 CrossRef
• Pittas AG, Dawson-Hughes B (2010) Vitamin D and diabetes. J Steroid Biochem Mol Biol 121:425–429 CrossRef
• Cantorna MT, Mahon BD (2005) D-hormone and the immune system. J Rheumatol Suppl 76:11–20
• Holick MF (2011) Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets 12:4–18 CrossRef
• Arnson Y, Amital H, Agmon-Levin N et al (2011) Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev 10:490–494 CrossRef
• Hajas A, Sandor J, Csathy L et al (2011) Vitamin D insufficiency in a large MCTD population. Autoimmun Rev 10:317–324 CrossRef
• Holick MF, MacLaughlin JA, Clark MB et al (1980) Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science 210:203–205 CrossRef
• Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231
• Haussler MR, Whitfield GK, Haussler CA et al (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 13:325–349 CrossRef
• Smolders J, Peelen E, Thewissen M et al (2009) The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev 8:621–626 CrossRef
• Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338:143–156 CrossRef
• Colin EM, Weel AE, Uitterlinden AG et al (2000) Consequences of vitamin D receptor gene polymorphisms for growth inhibition of cultured human peripheral blood mononuclear cells by 1, 25-dihydroxyvitamin D3. Clin Endocrinol (Oxf) 52:211–216 CrossRef
• van Etten E, Verlinden L, Giulietti A et al (2007) The vitamin D receptor gene FokI polymorphism: functional impact on the immune system. Eur J Immunol 37:395–405 CrossRef
• Orton SM, Morris AP, Herrera BM et al (2008) Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis. Am J Clin Nutr 88:441–447
• Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R (2009) Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol 207:117–121 CrossRef
• Monticielo OA, Brenol JC, Chies JA et al (2012) The role of BsmI and FokI vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D in Brazilian patients with systemic lupus erythematosus. Lupus 21:43–52 CrossRef
• Ban Y, Taniyama M, Yanagawa T et al (2001) Vitamin D receptor initiation codon polymorphism influences genetic susceptibility to type 1 diabetes mellitus in the Japanese population. BMC Med Genet 2:7 CrossRef
• Fassbender WJ, Goertz B, Weismuller K et al (2002) VDR gene polymorphisms are overrepresented in german patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism. Horm Metab Res 34:330–337 CrossRef
• Gyorffy B, Vasarhelyi B, Krikovszky D et al (2002) Gender-specific association of vitamin D receptor polymorphism combinations with type 1 diabetes mellitus. Eur J Endocrinol 147:803–808 CrossRef
• Audi L, Marti G, Esteban C et al (2004) VDR gene polymorphism at exon 2 start codon (FokI) may have influenced Type 1 diabetes mellitus susceptibility in two Spanish populations. Diabet Med 21:393–394 CrossRef
• Capoluongo E, Pitocco D, Concolino P et al (2006) Slight association between type 1 diabetes and “ff” VDR FokI genotype in patients from the Italian Lazio Region. Lack of association with diabetes complications. Clin Biochem 39:888–892 CrossRef
• Lemos MC, Fagulha A, Coutinho E et al (2008) Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population. Hum Immunol 69:134–138 CrossRef
• Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E (2009) Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol 133:276–281 CrossRef
• Gogas Yavuz D, Keskin L, Kiyici S et al (2011) Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients. Acta Diabetol 48:329–336 CrossRef
• Mohammadnejad Z, Ghanbari M, Ganjali R et al (2012) Association between vitamin D receptor gene polymorphisms and type 1 diabetes mellitus in Iranian population. Mol Biol Rep 39:831–837 CrossRef
• Huang CM, Wu MC, Wu JY, Tsai FJ (2002) No association of vitamin D receptor gene start codon fok 1 polymorphisms in Chinese patients with systemic lupus erythematosus. J Rheumatol 29:1211–1213
• Tajouri L, Ovcaric M, Curtain R et al (2005) Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population. J Neurogenet 19:25–38 CrossRef
• Simon KC, Munger KL, Xing Y, Ascherio A (2010) Polymorphisms in vitamin D metabolism related genes and risk of multiple sclerosis. Mult Scler 16:133–138 CrossRef
• Fukazawa T, Yabe I, Kikuchi S et al (1999) Association of vitamin D receptor gene polymorphism with multiple sclerosis in Japanese. J Neurol Sci 166:47–52 CrossRef
• Chang TJ, Lei HH, Yeh JI et al (2000) Vitamin D receptor gene polymorphisms influence susceptibility to type 1 diabetes mellitus in the Taiwanese population. Clin Endocrinol (Oxf) 52:575–580 CrossRef
• Ozaki Y, Nomura S, Nagahama M, Yoshimura C, Kagawa H, Fukuhara S (2000) Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus. Nephron 85:86–91 CrossRef
• Niino M, Fukazawa T, Yabe I, Kikuchi S, Sasaki H, Tashiro K (2000) Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J Neurol Sci 177:65–71 CrossRef
• Huang CM, Wu MC, Wu JY, Tsai FJ (2002) Association of vitamin D receptor gene BsmI polymorphisms in Chinese patients with systemic lupus erythematosus. Lupus 11:31–34 CrossRef
• Taverna MJ, Sola A, Guyot-Argenton C et al (2002) Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy. Diabetologia 45:436–442 CrossRef
• Shimada A, Kanazawa Y, Motohashi Y et al (2008) Evidence for association between vitamin D receptor BsmI polymorphism and type 1 diabetes in Japanese. J Autoimmun 30:207–211 CrossRef
• Luo XY, Yang MH, Wu FX et al (2012) Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population. Lupus 21:53–59 CrossRef
• Sakulpipatsin W, Verasertniyom O, Nantiruj K, Totemchokchyakarn K, Lertsrisatit P, Janwityanujit S (2006) Vitamin D receptor gene BsmI polymorphisms in Thai patients with systemic lupus erythematosus. Arthritis Res Ther 8:R48 CrossRef
• Smolders J, Damoiseaux J, Menheere P, Tervaert JW, Hupperts R (2009) Association study on two vitamin D receptor gene polymorphisms and vitamin D metabolites in multiple sclerosis. Ann N Y Acad Sci 1173:515–520 CrossRef
• Abbasi M, Rezaieyazdi Z, Afshari JT, Hatef M, Sahebari M, Saadati N (2010) Lack of association of vitamin D receptor gene BsmI polymorphisms in patients with systemic lupus erythematosus. Rheumatol Int 30:1537–1539 CrossRef
• Sioka C, Papakonstantinou S, Markoula S et al (2011) Vitamin D receptor gene polymorphisms in multiple sclerosis patients in northwest Greece. J Negat Results Biomed 10:3 CrossRef
• Cox MB, Ban M, Bowden NA, Baker A, Scott RJ, Lechner-Scott J (2012) Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis. Mult Scler 18:16–22 CrossRef
• Adorini L, Penna G (2008) Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 4:404–412 CrossRef
• Szodoray P, Nakken B, Gaal J et al (2008) The complex role of vitamin D in autoimmune diseases. Scand J Immunol 68:261–269 CrossRef
• Cutolo M, Pizzorni C, Sulli A (2011) Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev 11:84–87 CrossRef
• Peelen E, Knippenberg S, Muris AH et al (2011) Effects of vitamin D on the peripheral adaptive immune system: a review. Autoimmun Rev 10:733–743 CrossRef
• Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM (1983) Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 57:1308–1310 CrossRef
• Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221:1181–1183 CrossRef
• Veldman CM, Cantorna MT, DeLuca HF (2000) Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys 374:334–338 CrossRef
• Deluca HF, Cantorna MT (2001) Vitamin D: its role and uses in immunology. FASEB J 15:2579–2585 CrossRef
• Alroy I, Towers TL, Freedman LP (1995) Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. Mol Cell Biol 15:5789–5799
• Lemire JM, Archer DC, Beck L, Spiegelberg HL (1995) Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 125:1704S–1708S
• Cippitelli M, Santoni A (1998) Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 28:3017–3030 CrossRef
• Rigby WF, Stacy T, Fanger MW (1984) Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J Clin Invest 74:1451–1455 CrossRef
• Lemire JM, Adams JS, Kermani-Arab V, Bakke AC, Sakai R, Jordan SC (1985) 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J Immunol 134:3032–3035
• Reichel H, Koeffler HP, Tobler A, Norman AW (1987) 1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci U S A 84:3385–3389 CrossRef
• Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A (2001) 1Alpha,25-dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980
• Gorman S, Kuritzky LA, Judge MA et al (2007) Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+ CD25+ cells in the draining lymph nodes. J Immunol 179:6273–6283
• Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM (2008) Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 324:23–33 CrossRef
• Yu S, Cantorna MT (2008) The vitamin D receptor is required for iNKT cell development. Proc Natl Acad Sci U S A 105:5207–5212 CrossRef
• Broux B, Pannemans K, Zhang X et al (2012) CX(3)CR1 drives cytotoxic CD4(+)CD28(−) T cells into the brain of multiple sclerosis patients. J Autoimmun 38:10–19 CrossRef
• Luckey D, Bastakoty D, Mangalam AK (2011) Role of HLA class II genes in susceptibility and resistance to multiple sclerosis: studies using HLA transgenic mice. J Autoimmun 37:122–128 CrossRef
• Moroni L, Bianchi I, Lleo A (2012) Geoepidemiology, gender and autoimmune disease. Autoimmun Rev 11:A386–A392 CrossRef
• Sellner J, Kraus J, Awad A, Milo R, Hemmer B, Stuve O (2011) The increasing incidence and prevalence of female multiple sclerosis–a critical analysis of potential environmental factors. Autoimmun Rev 10:495–502 CrossRef
• Soilu-Hanninen M, Airas L, Mononen I, Heikkila A, Viljanen M, Hanninen A (2005) 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler 11:266–271 CrossRef
• Correale J, Ysrraelit MC, Gaitan MI (2009) Immunomodulatory effects of Vitamin D in multiple sclerosis. Brain 132:1146–1160 CrossRef
• Soilu-Hanninen M, Laaksonen M, Laitinen I, Eralinna JP, Lilius EM, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:152–157 CrossRef
• van der Mei IA, Ponsonby AL, Dwyer T et al (2007) Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 254:581–590 CrossRef
• Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R (2008) Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 14:1220–1224 CrossRef
• Hiremath GS, Cettomai D, Baynes M et al (2009) Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis. Mult Scler 15:735–740 CrossRef
• Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A (2006) Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296:2832–2838 CrossRef
• Kragt J, van Amerongen B, Killestein J et al (2009) Higher levels of 25-hydroxyvitamin D are associated with a lower incidence of multiple sclerosis only in women. Mult Scler 15:9–15 CrossRef
• de Boer IH, Sachs MC, Cleary PA et al. (2012) Circulating vitamin D metabolites and kidney disease in type 1 diabetes. J Clin Endocrinol Metab 97(12):4780–4788
• Borkar VV, Devidayal, Verma S, Bhalla AK (2010) Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Pediatr Diabetes 11:345–350 CrossRef
• Singh DK, Winocour P, Summerhayes B, Viljoen A, Sivakumar G, Farrington K (2009) Are low erythropoietin and 1,25-dihydroxyvitamin D levels indicative of tubulo-interstitial dysfunction in diabetes without persistent microalbuminuria? Diabetes Res Clin Pract 85:258–264 CrossRef
• Bener A, Alsaied A, Al-Ali M et al (2009) High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children. Acta Diabetol 46:183–189 CrossRef
• Littorin B, Blom P, Scholin A et al (2006) Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia 49:2847–2852 CrossRef
• Bogaczewicz J, Sysa-Jedrzejowska A, Arkuszewska C et al (2012) Vitamin D status in systemic lupus erythematosus patients and its association with selected clinical and laboratory parameters. Lupus 21:477–484 CrossRef
• Kim HA, Sung JM, Jeon JY, Yoon JM, Suh CH (2011) Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus. Rheumatol Int 31:1189–1194 CrossRef
• Amital H, Szekanecz Z, Szucs G et al (2010) Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis 69:1155–1157 CrossRef
• Wright TB, Shults J, Leonard MB, Zemel BS, Burnham JM (2009) Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. J Pediatr 155:260–265 CrossRef
• Borba VZ, Vieira JG, Kasamatsu T, Radominski SC, Sato EI, Lazaretti-Castro M (2009) Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporos Int 20:427–433 CrossRef
• Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C (2008) Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 47:920–923 CrossRef
• Cantorna MT (2006) Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol 92:60–64 CrossRef
• Nordvik I, Myhr KM, Nyland H, Bjerve KS (2000) Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand 102:143–149 CrossRef
• Achiron A, Barak Y, Miron S, Izhak Y, Faibel M, Edelstein S (2003) Alfacalcidol treatment in multiple sclerosis. Clin Neuropharmacol 26:53 CrossRef
• Wingerchuk DM, Lesaux J, Rice GP, Kremenchutzky M, Ebers GC (2005) A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 76:1294–1296 CrossRef
• Li X, Liao L, Yan X et al (2009) Protective effects of 1-alpha-hydroxyvitamin D3 on residual beta-cell function in patients with adult-onset latent autoimmune diabetes (LADA). Diabetes Metab Res Rev 25:411–416 CrossRef
• Pitocco D, Crino A, Di Stasio E et al (2006) The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset type 1 diabetes (IMDIAB XI). Diabet Med 23:920–923 CrossRef
• Ruiz-Irastorza G, Gordo S, Olivares N, Egurbide MV, Aguirre C (2010) Changes in vitamin D levels in patients with systemic lupus erythematosus: effects on fatigue, disease activity, and damage. Arthritis Care Res (Hoboken) 62:1160–1165 CrossRef
• Antico A, Tampoia M, Tozzoli R, Bizzaro N (2012) Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature. Autoimmun Rev 12:127–136.com/article/10.1007%2Fs12016-013-8361-3 |CrossRef]
• Roy E, Leduc M, Guegan S et al (2011) Specific maternal microchimeric T cells targeting fetal antigens in beta cells predispose to auto-immune diabetes in the child. J Autoimmun 36:253–262 CrossRef
• Bogdanos DP, Smyk DS, Rigopoulou EI et al (2012) Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun 38:J156–J169 CrossRef
• Staples JA, Ponsonby AL, Lim LL, McMichael AJ (2003) Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence. Environ Health Perspect 111:518–523 CrossRef
• Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503 CrossRef
• Agmon-Levin N, Mosca M, Petri M, Shoenfeld Y (2012) Systemic lupus erythematosus one disease or many? Autoimmun Rev 11:593–595 CrossRef
• Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME (2010) The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev 9:A277–A287 CrossRef
• Fu SM, Deshmukh US, Gaskin F (2011) Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. J Autoimmun 37:104–112 CrossRef
• Lehmann P, Homey B (2009) Clinic and pathophysiology of photosensitivity in lupus erythematosus. Autoimmun Rev 8:456–461 CrossRef
• Breslin LC, Magee PJ, Wallace JM, McSorley EM (2011) An evaluation of vitamin D status in individuals with systemic lupus erythematosus. Proc Nutr Soc 70:399–407 CrossRef

---

See also Vitamin D Life

• All items in category Inflammation and Vitamin DYou do not have the permission that is needed to use this feature items
• Autoimmune diseases fought by vitamin D – literature review Dec 2012
• Autoimmune category listing with associated searches
• Video by Dr. Coimbra – 95 percent of auto-immune cured with vitamin D in high doses - April 2014
• Review of Autoimmune diseases, solar radiation and vitamin D – Schwalfenberg 2012
• nnate and adaptive immune systems probably helped by vitamin D – Oct 2014
• Brazillian petition to permit high vitamin D doses for autoimune diseases – Aug 2014
• Autoimmunity and Optimal Vitamin-D – Stochastic Chemical Dynamic correlation – June 2014