Role of vitamin D deficiency in systemic lupus erythematosus incidence and aggravation

Tohid Hassanalilou, Leila Khalili, Saeid Ghavamzadeh, Ali Shokri, Laleh Payahoo, Yaser Khaje Bishak, Tohid Hassanalilou, Leila Khalili, Saeid Ghavamzadeh, Ali Shokri, Laleh Payahoo, Yaser Khaje Bishak

Abstract

Vitamin D is one of the main groups of sterols; playing an important role in phospho-calcic metabolism. The conversion of 7-dehydrocholesterol to pre- vitamin D3 in the skin, through solar ultraviolet B radiation, is the main source of vitamin D. Since lupus patients are usually photosensitive, the risk of developing vitamin D deficiency in is high in this population. Although evidences showed the connotation between systemic lupus erythematosus (SLE) and vitamin D through which SLE can lead to lower vitamin D levels, it is also important to consider the possibility that vitamin D deficiency may have a causative role in SLE etiology. This paper analyzes existing data from various studies to highlight the role of vitamin D deficiency in SLE occurrence and aggravation and the probable efficacy of vitamin D supplementation on SLE patients. We searched "Science Direct" and "Pub Med" using "Vitamin D" and "SLE" for finding the studies focusing on the association between vitamin D deficiency and SLE incidence and consequences. Evidences show that vitamin D plays an important role in the pathogenesis and progression of SLE and vitamin D supplementation seems to ameliorate inflammatory and hemostatic markers; so, can improve clinical subsequent.

Keywords: SLE aggravation; SLE incidence; Systemic lupus erythematosus; Vitamin D deficiency.

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

There is no informed consent required for this manuscript.

Human and animal rights

There are no human or animal rights to be considered in this manuscript.

Figures

Fig. 1
Fig. 1
The two-sided relation between vitamin D and SLE showing that low levels of vitamin D resulted from SLE and SLE complications come from vitamin D deficiency
Fig. 2
Fig. 2
The beneficial effects of vitamin D in prevention and/or control of SLE

References

    1. Agmon-Levin N, Mosca M, Petri M, Shoenfeld Y. Systemic lupus erythematosus one disease or many? Autoimmun Rev. 2012;11:593–595.
    1. Fu SM, Deshmukh US, Gaskin F. Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. J Autoimmun. 2011;37:104–112.
    1. Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev. 2010;9:A277–A287.
    1. Yang C-Y, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45:217–226.
    1. Kamen DL. Vitamin D in lupus: new kid on the block? Bull Hosp Jt Dis. 2010;68:218.
    1. Pakpoor J, Pakpoor J. Vitamin d deficiency and systemic lupus erythematosus: cause or consequence. Oman Med J. 2013;28:295.
    1. Sakthiswary R, Raymond AA. The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review. PLoS One. 2013;8:e55275.
    1. Mok CC. Vitamin D and systemic lupus erythematosus: an update. Expert Rev Clin Immunol. 2013;9:453–463.
    1. Borba V, Vieira J, Kasamatsu T, Radominski S, Sato E, Lazaretti-Castro M. Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporis Int. 2009;20:427–433.
    1. Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, et al. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777–783.
    1. Maruotti N, Cantatore FP. Vitamin D and the immune system. J Rheumatol. 2010;37:491–495.
    1. Iruretagoyena M, Hirigoyen D, Naves R, Burgos PI. Immune response modulation by vitamin D: role in systemic lupus erythematosus. Front Immunol. 2015;6:513.
    1. Cutolo M, Otsa K, Paolino S, Yprus M, Veldi T, Seriolo B. Vitamin D involvement in rheumatoid arthritis and systemic lupus erythaematosus. Ann Rheum Dis. 2009;68:446.
    1. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A. 1α, 25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells. J Immunol. 2001;167:4974–4980.
    1. Koizumi T, Nakao Y, Matsui T, Nakagawa T, Matsuda S, Komoriya K, et al. Effects of corticosteroid and 1,24R-dihydroxy-vitamin D3 administration on lymphoproliferation and autoimmune disease in MRL/MP-lpr/lpr mice. Int Arch Allergy Immunol. 1985;77:396–404.
    1. Attar SM, Siddiqui AM. Vitamin d deficiency in patients with systemic lupus erythematosus. Oman Med J. 2013;28:42–47.
    1. Handel AE, Handunnetthi L, Ebers GC, Ramagopalan SV. Type 1 diabetes mellitus and multiple sclerosis: common etiological features. Nat Rev Endocrinol. 2009;5:655–664.
    1. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–2838.
    1. Penna G, Adorini L. 1α,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol. 2000;164:2405–2411.
    1. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007;179:1634–1647.
    1. Van Halteren AG, Tysma OM, van Etten E, Mathieu C, Roep BO. 1α,25-Dihydroxyvitamin D 3 or analogue treated dendritic cells modulate human autoreactive T cells via the selective induction of apoptosis. J Autoimmun. 2004;23:233–239.
    1. Rönnblom L, Pascual V. The innate immune system in SLE: type I interferons and dendritic cells. Lupus. 2008;17:394–399.
    1. Disanto G, Chaplin G, Morahan JM, Giovannoni G, Hyppönen E, Ebers GC, et al. Month of birth, vitamin D and risk of immune-mediated disease: a case control study. BMC Med. 2012;10:1.
    1. Ramagopalan SV, Heger A, Berlanga AJ, Maugeri NJ, Lincoln MR, Burrell A, et al. A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Res. 2010;20:1352–1360.
    1. K-i Miyamoto, Kesterson RA, Yamamoto H, Taketani Y, Nishiwaki E, Tatsumi S, et al. Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol. 1997;11:1165–1179.
    1. Morrison NA, Yeoman R, Kelly PJ, Eisman JA. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci. 1992;89:6665–6669.
    1. Lee YH, Bae S-C, Choi SJ, Ji JD, Song GG. Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep. 2011;38:3643–3651.
    1. Ruiz-Irastorza G, Egurbide M, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology. 2008;47:920–923.
    1. Bultink IE, Lems WF, Kostense PJ, Dijkmans BA, Voskuyl AE. Prevalence of and risk factors for low bone mineral density and vertebral fractures in patients with systemic lupus erythematosus. Arthritis Rheum. 2005;52:2044–2050.
    1. Müller K, Kriegbaum N, Baslund B, Sørensen O, Thymann M, Bentzen K. Vitamin D3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D3 in patients with systemic lupus erythematosus. Clin Rheumatol. 1995;14:397–400.
    1. Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs J, et al. Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. J Rheumatol. 2001;28:2535–2539.
    1. Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev. 2006;5(2):114–117.
    1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–281.
    1. Janssen HC, Samson MM, Verhaar HJ. Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr. 2002;75:611–615.
    1. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79:362–371.
    1. Mok C, Birmingham D, Ho L, Hebert L, Song H, Rovin B. Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus: a comparison with anti-dsDNA and anti-C1q. Lupus. 2012;21:36–42.
    1. Amital H, Szekanecz Z, Szücs G, Danko K, Nagy E, Csepany T, et al. 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. 2010;69:1155–1157.
    1. Mok CC, Birmingham DJ, Leung HW, Hebert LA, Song H, Rovin BH. Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis. Rheumatology. 2012;51:644–652.
    1. Yap K, Northcott M, Hoi AB, Morand E, Nikpour M. Association of low vitamin D with high disease activity in an Australian systemic lupus erythematosus cohort. Lupus Sci Med. 2015;2:e000064.
    1. Holick MF. High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006;81:353–373.
    1. Tench C, McCurdie I, McCarthy J, White P, D’Cruz D. The assessment of aerobic capacity in a group of patients with SLE and its association with fatigue, sleep quality and disease activity. Arthritis Rheum. 1998;9:S332.
    1. Ramsey-Goldman R, Schilling EM, Dunlop D, Langman C, Greenland P, Thomas RJ, et al. A pilot study on the effects of exercise in patients with systemic lupus erythematosus. Arthr Care Res. 2000;13:262–269.
    1. Kiani AN, Petri M. Quality-of-life measurements versus disease activity in systemic lupus erythematosus. Curr Rheumatol Rep. 2010;12:250–258.
    1. Zonana-Nacach A, Roseman JM, McGwin G, Friedman AW, Baethge BA, Reveille JD. Systemic lupus erythematosus in three ethnic groups. VI: factors associated with fatigue within 5 years of criteria diagnosis. Lupus. 2000;9:101–109.
    1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46:1121–1123.
    1. Bischoff H, Borchers M, Gudat F, Duermueller U, Theiler R, Stähelin H, et al. In situ detection of 1,25-dihydroxyvitamin D receptor in human skeletal muscle tissue. Histochem J. 2001;33:19–24.
    1. Simpson R, Thomas G, Arnold A. Identification of 1,25-dihydroxyvitamin D3 receptors and activities in muscle. J Biol Chem. 1985;260:8882–8891.
    1. Sato Y, Iwamoto J, Kanoko T, Satoh K. Low-dose vitamin D prevents muscular atrophy and reduces falls and hip fractures in women after stroke: a randomized controlled trial. Cerebrovasc Dis. 2005;20:187–192.
    1. Finol H, Montagnani S, Marquez A, Montes DO, Müller B. Ultrastructural pathology of skeletal muscle in systemic lupus erythematosus. J Rheumatol. 1990;17:210–219.
    1. Stockton K, Kandiah D, Paratz JD, Bennell K. Fatigue, muscle strength and vitamin D status in women with systemic lupus erythematosus compared with healthy controls. Lupus. 2012;21:271–278.
    1. Tench C, McCurdie I, White P, D’Cruz D. The prevalence and associations of fatigue in systemic lupus erythematosus. Rheumatology. 2000;39:1249–1254.
    1. Ruiz-Irastorza G, Gordo S, Olivares N, Egurbide MV, Aguirre C. Changes in vitamin D levels in patients with systemic lupus erythematosus: effects on fatigue, disease activity, and damage. Arthr Care Res. 2010;62:1160–1165.
    1. Rhew EY, Lee C, Eksarko P, Dyer AR, Tily H, Spies S, et al. Homocysteine, bone mineral density, and fracture risk over 2 years of followup in women with and without systemic lupus erythematosus. J Rheumatol. 2008;35:230–236.
    1. Kalla AA, Fataar AB, Jessop SJ, Bewerunge L. Loss of trabecular bone mineral density in systemic lupus erythematosus. Arthr Rheum. 1993;36:1726–1734.
    1. Cunnane G, Lane NE. Steroid-induced osteoprosis in systemic lupus erythematosus. Rheum Dis Clin N Am. 2000;26:311–329.
    1. Sen D, Keen R. Osteoporosis in systemic lupus erythematosus: prevention and treatment. Lupus. 2001;10:227–232.
    1. Aringer M, Smolen J. Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. Lupus. 2004;13:344–347.
    1. Gabay C, Cakir N, Moral F, Roux-Lombard P, Meyer O, Dayer J, et al. Circulating levels of tumor necrosis factor soluble receptors in systemic lupus erythematosus are significantly higher than in other rheumatic diseases and correlate with disease activity. J Rheumatol. 1997;24:303–308.
    1. Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC. Benefit–risk assessment of vitamin D supplementation. Osteoporis Int. 2010;21:1121–1132.
    1. Robinson AB, Thierry-Palmer M, Gibson KL, Rabinovich CE. Disease activity, proteinuria, and vitamin D status in children with systemic lupus erythematosus and juvenile dermatomyositis. J Pediatr. 2012;160:297–302.
    1. Robinson AB, Rabinovich CE. Hypovitaminosis D is prevalent despite vitamin D supplementation in pediatric systemic lupus erythematosus. In: Robinson AB, Rabinovich CE, editors. Arthritis Rheumatism. 58. 2008. p. 3982.
    1. Petri M, Bello KJ, Fang H, Magder LS. Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio. Arthr Rheum. 2013;65:1865–1871.
    1. Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int. 2005;68:2823–2828.
    1. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, et al. Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol. 2010;106:963–968.
    1. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004) Am J Cardiol. 2008;102:1540–1544.
    1. Baz-Hecht M, Goldfine AB. The impact of vitamin D deficiency on diabetes and cardiovascular risk. Curr Opin Endocrinol Diabetes Obes. 2010;17:113–119.
    1. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007;167:1159–1165.
    1. Vanga SR, Good M, Howard PA, Vacek JL. Role of vitamin D in cardiovascular health. Am J Cardiol. 2010;106:798–805.
    1. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthr Rheum. 1997;40:1725.
    1. Mok C. Accelerated atherosclerosis, arterial thromboembolism, and preventive strategies in systemic lupus erythematosus. Scand J Rheumatol. 2006;35:85–95.
    1. Wu PW, Rhew EY, Dyer AR, Dunlop DD, Langman CB, Price H, et al. 25-hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus. Arthr Care Res. 2009;61:1387–1395.
    1. Ezzat Y, Sayed S, Gaber W, Mohey AM, Kassem TW. 25-Hydroxy vitamin D levels and its relation to disease activity and cardiovascular risk factors in women with systemic lupus erythematosus. Egypt Rheumatol. 2011;33:195–201.
    1. Petri M, Bello KJ. Vitamin D levels are positively associated with complement among patients with SLE. Arthritis Rheum. 2010;62:1180.
    1. Iseki K, Tatsuta M, Uehara H, Iishi H, Yano H, Sakai N, et al. Inhibition of angiogenesis as a mechanism for inhibition by Lα-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in Wistar rats. Int J Cancer. 1999;81:730–733.
    1. Mantell D, Owens P, Bundred N, Mawer E, Canfield A. 1α,25-dihydroxyvitamin D3 inhibits angiogenesis in vitro and in vivo. Circ Res. 2000;87:214–220.
    1. Pálmer HG, González-Sancho JM, Espada J, Berciano MT, Puig I, Baulida J, et al. Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling. J Cell Biol. 2001;154:369–388.
    1. Fujioka T, Suzuki Y, Okamoto T, Mastushita N, Hasegawa M, Omori S. Prevention of renal cell carcinoma by active vitamin D3. World J Surg. 2000;24:1205–1210.
    1. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252–261.
    1. Lipkin M, Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985;313:1381–1384.
    1. Holt PR, Arber N, Halmos B, Forde K, Kissileff H, McGlynn KA, et al. Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D. Cancer Epidemiol Biomark Prev. 2002;11:113–119.
    1. Campbell MJ, Reddy GS, Koeffler HP. Vitamin D3 analogs and their 24-Oxo metabolites equally inhibit clonal proliferation of a variety of cancer cells but have differing molecular effects. J Cell Biochem. 1997;66:413–425.
    1. Brenner B, Russell N, Albrecht S, Davies R. The effect of dietary vitamin D 3 on the intracellular calcium gradient in mammalian colonic crypts. Cancer Lett. 1998;127:43–53.
    1. Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW, Jäättelä M. Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D compounds in breast cancer cells. J Biol Chem. 2002;277:30738–30745.
    1. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85:1586–1591.
    1. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167:1730–1737.
    1. Terrier B, Derian N, Schoindre Y, Chaara W, Geri G, Zahr N, et al. Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthr Res Ther. 2012;14:1.
    1. Abou-Raya A, Abou-Raya S, Helmii M. The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol. 2013;40:265–272.
    1. Marinho António, Carvalho Cláudia, Boleixa Daniela, Bettencourt Andreia, Leal Bárbara, Guimarães Judite, Neves Esmeralda, Oliveira José Carlos, Almeida Isabel, Farinha Fátima, Costa Paulo P., Vasconcelos Carlos, Silva Berta M. Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort. Immunologic Research. 2016;65(1):197–206.
    1. Tabasi N, Rastin M, Mahmoudi M, Ghoryani M, Mirfeizi Z, Rabe SZT, et al. Influence of vitamin D on cell cycle, apoptosis, and some apoptosis related molecules in systemic lupus erythematosus. Iran J Basic Med Sci. 2015;18:1107.
    1. Reynolds JA, Haque S, Williamson K, Ray DW, Alexander MY, Bruce IN. Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus. Sci Rep. 2016;2016:6.
    1. Lemire JM, Ince A, Takashima M. 1,25-dihydroxyvitamin D3 attenuates of expression of experimental murine lupus of MRL/1 mice. Autoimmunity. 1992;12:143–148.
    1. Yap KS, Morand EF. Vitamin D and systemic lupus erythematosus: continued evolution. Int J Rheum Dis. 2015;18:242–249.
    1. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999;69:842–856.
    1. Nowson CA, McGrath JJ, Ebeling PR, Haikerwal A, Daly RM, Sanders KM, et al. Vitamin D and health in adults in Australia and New Zealand: a position statement. Med J Aust. 2012;196:686–687.
    1. Vero V, Gasbarrini A. The EFSA health claims ‘learning experience’. Int J Food Sci Nutr. 2012;63:14–16.

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