DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20183927

Vitamin D levels in systematic lupus erythematosus patients: association with disease activity index and interferon alpha

Afsaneh Enteshari-moghaddam, Gholamreza Ravaei, Ahad Azami

Abstract


Background: In different studies the correlation between systemic lupus erythematosus (SLE) and disease activity with vitamin D has been shown. The role of different interferons especially interferon alpha (IFN-α) in lupus pathogenesis have been previously shown. Considering the role of vitamin D and IFN-α, it is possible that these two could demonstrate the SLE activity. This study aimed to investigate the association between vitamin D levels and IFN-α with disease activity index in Ardabil city SLE patients.

Methods: In this case control study, 50 SLE patients and 50 age and sex matched healthy subjects were recruited. Patients had serum 25-OH Vitamin D concentration and disease activity recorded. Vitamin D and IFN-α levels were compared between two groups and also, levels of anti-dsDNA, and SLEDAI in case group was measured. Statistical methods were used to determine the correlation between vitamin D and IFN-α with disease activity index at baseline.

Results: Vitamin D deficiency (<40 nmol/L) was detected in 20% of SLE patients. Vitamin D level in case group significantly lower than control group (23.94±11.93 vs. 29.10±11.40 ng/ml, p=0.02). The IFN-α amount in case group significantly upper than control group (396.60±54.73 vs. 200.38±14.42, p=0.001). There was significantly negative correlation between vitamin D with IFN-α (r=-0.413, p=0.003), SLEDAI (r=-0.492, p<0.001) and anti-dsDNA (r=-0.417, p=0.003). There was positive correlation between IFN-α with SLEDAI (r=0.358, p=0.01) and anti-dsDNA (p=0.297, p=0.03).

Conclusions: Results showed that the low vitamin D was associated with a higher disease activity in SLE patients. Also, it seems that, the improvement of vitamin D levels by decreasing IFN-α could help in controlling disease activity in future.


Keywords


Disease activity, Interferon alpha, Systemic Lupus Erythematosus, Vitamin D

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References


Crispín JC, Liossis SN, Kis-Toth K, Lieberman LA, Kyttaris VC, Juang YT, et al. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends in molecular medicine. 2010 Feb 1;16(2):47-57.

Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365:2110-21.

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. Arthritis Rheumatism. 2013 Jul;65(7):1865-71.

Borba VZ, Vieira JG, Kasamatsu T, Radominski SC, Sato EI, Lazaretti-Castro M. Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporosis Int. 2009 Mar 1;20(3):427-33.

Hamza RT, Awwad KS, Ali MK, Hamed AI. Reduced serum concentrations of 25-hydroxy vitamin D in Egyptian patients with systemic lupus erythematosus: relation to disease activity. Medical Sci Monitor: Int Med J Experiment Clin Res. 2011;17(12):CR711.

Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y. Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. J Rheumatol. 2009;36:1924-9.

Yap KS, Morand EF. Vitamin D and systemic lupus erythematosus: continued evolution. Int J Rheumatic Dis. 2015 Feb;18(2):242-9.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.

Holick MF. Vitamin D: important for prevention of osteoporosis, cardio-vascular heart disease, type 1 diabetes, autoimmune diseases, and some cancers. South Med J. 2005;98(10):10247.

Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: modulator of the immune system. Current opinion in pharmacology. 2010 Aug 1;10(4):482-96.

Borges MC, Martini LA, Rogero MM. Current perspectives on vitamin D, immune system, and chronic diseases. Nutrition. 2011;27:399-404.

Cutolo M, Pizzorni C, Sulli A. Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmunity Rev. 2011 Dec 1;11(2):84-7.

Shoenfeld Y, Giacomelli R, Azrielant S, Berardicurti O, Reynolds JA, Bruce IN. Vitamin D and systemic lupus erythematosus-The hype and the hope. Autoimmunity reviews. 2017 Nov 3.

Holick MF. Vitamin D: A millenium perspective. J Cellular Biochem. 2003 Feb 1;88(2):296-307.

Niewold TB, Clark DN, Salloum R, Poole BD. Interferon alpha in systemic lupus erythematosus. BioMed Res Int. 2010.

Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Activation of the interferon‐α pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheumatism. 2005 May 1;52(5):1491-503.

Dall’Era MC, Cardarelli PM, Preston BT, Witte A, Davis JC. Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheumatic Dis. 2005 Dec 1;64(12):1692-7.

Feng X, Wu H, Grossman JM, Hanvivadhanakul P, FitzGerald JD, Park GS, et al. Association of increased interferon‐inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheumatism. 2006 Sep;54(9):2951-62.

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. 2012:111594.

Gurion R, Tangpricha V, Yow E, Schanberg LE, McComsey GA, Robinson AB. Avascular necrosis in pediatric systemic lupus erythematosus: a brief report and review of the literature. Pediatr Rheumatol. 2015 Dec;13(1):13.

Piantoni S, Andreoli L, Scarsi M, Zanola A, Dall’Ara F, Pizzorni C, et al. Phenotype modifications of T-cells and their shift toward a Th2 response in patients with systemic lupus erythematosus supplemented with different monthly regimens of vitamin D. Lupus. 2015 Apr;24(4-5):490-8.

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. Arthritis Rheumatism. 2013 Jul;65(7):1865-71.

Lima GL, Paupitz J, Aikawa NE, Takayama L, Bonfa E, Pereira RM. Vitamin D supplementation in adolescents and young adults with juvenile systemic lupus erythematosus for improvement in disease activity and fatigue scores: a randomized, double‐blind, placebo‐controlled trial. Arthritis Care Res. 2016 Jan;68(1):91-8.

Mandal M, Tripathy R, Panda AK, Pattanaik SS, Dakua S, Pradhan AK, Chakraborty S, Ravindran B, Das BK. Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha. Arthritis Res Therapy. 2014 Feb;16(1):R49.

Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmunity Rev. 2006 Feb 1;5(2):114-7.

Cutolo M, Otsa K. Vitamin D, immunity and lupus. Lupus. 2008 Jan;17(1):6-10.

Heshmat R, Mohammad K, Majdzadeh SR, Forouzanfar MH, Bahrami A, et al. Vitamin D deficiency in Iran: A multi-center study among different urban areas. Iran J Public Health. 2008 Jan 1;37(suppl).

Saedinea A, Larijani B, Jalalinea S, Farzadfar F, Keshtkar F, Rezae A. Evaloation of prevalence deficiency of vitamin D in Iranian population the province during 1990-2010. Iran J Diabetes Metab. 2013;12(6):574-84.

Hashemipour S, Larijani B, Adibi H, Javadi E, Sedaghat M, Pajouhi M, et al. Vitamin D deficiency and causative factors in the population of Tehran. BMC Public Health. 2004 Dec;4(1):38.

Alizadeh Z, Hlbchy F, RadjabianTabesh M. The prevalence of vitamin D deficiency in individuals with a BMI higher than25 kg /m and its association with demographic and anthropometric indices. Tehran Univ Med J (TUMJ). 2015;73(6):447-55.

Hovsepian S, Amini M, Aminorroaya A, Amini P, Iraj B. Prevalence of vitamin D deficiency among adult population of Isfahan City, Iran. J Health Popul Nutrit. 2011 Apr;29(2):149.

Niafar M, Bahrami A, Aliasgharzadeh A, Aghamohammadzadeh N, Najafipour F, Mobasseri M. Vitamin D status in healthy postmenopausal Iranian women. J Res Med Sci. 2009 May;14(3):171.

Sumethkul K, Boonyaratavej S, Kitumnuaypong T, Angthararuk S, Cheewasat P, Manadee N, et al. The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus. Rheumatol Int. 2013 Jun 1;33(6):1461-7.

Toloza SM, Cole DE, Gladman DD, Ibanez D, Urowitz MB. Vitamin D insufficiency in a large female SLE cohort. Lupus. 2010 Jan;19(1):13-9.

Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatol. 2008 Apr 14;47(6):920-3.

Müller K, Kriegbaum NJ, Baslund B, Sørensen OH, Thymann M, Bentzen K. Vitamin D 3 metabolism in patients with rheumatic diseases: low serum levels of 25-hydroxyvitamin D 3 in patients with systemic lupus erythematosus. Clin Rheumatol. 1995 Jul 1;14(4):397-400.

Chen TC, Chimeh F, Lu Z, Mathieu J, Person KS, Zhang A, et al. Factors that influence the cutaneous synthesis and dietary sources of vitamin D. Arch Biochem Biophysics. 2007 Apr 15;460(2):213-7.

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. Arthritis Res Therapy. 2012 Oct;14(5):R221.

Zhuang H, Narain S, Sobel E, Lee PY, Nacionales DC, Kelly KM, et al. Association of anti-nucleoprotein autoantibodies with upregulation of Type I interferon-inducible gene transcripts and dendritic cell maturation in systemic lupus erythematosus. Clin Immunol. 2005 Dec 1;117(3):238-50.

Adams JS, Hewison M. Update in vitamin D. The Journal of Clinical Endocrinol Metabol. 2010 Feb 1;95(2):471-8.

Kareem MIA, Mohammed RHA, Abozaid HSM, Rayan MM, Mohamed AM, et al. Hypo-vitaminosis D in Patients with Rheumatoid Arthritis, Systemic Lupus Erythematosus and Ankylosing Spondylitis. J Clin Cell Immunol. 2015;6:369.

Oke V, Brauner S, Larsson A, Gustafsson J, Zickert A, Gunnarsson I, et al. IFN-λ1 with Th17 axis cytokines and IFN-α define different subsets in systemic lupus erythematosus (SLE). Arthritis Res Therapy. 2017 Dec;19(1):139.

Jolly M, Francis S, Aggarwal R, Mikolaitis RA, Niewold TB, Chubinskaya S, et al. Serum free light chains, interferon-alpha, and interleukins in systemic lupus erythematosus. Lupus. 2014 Aug;23(9):881-8.

Ritterhouse LL, Crowe SR, Niewold TB, Kamen DL, Macwana SR, Roberts VC, et al. Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheumatic Dis. 2011 Sep 1;70(9):1569-74.