ROLE OF VITAMIN D IN SYSTEMIC LUPUS ERYTHEMATOSUS

INTRODUCTION
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown
origin, in which both genetic and environmental factors are involved. It can cause chronic
inflammation and damage in several tissues and organs. One such environmental factor is
vitamin D, a vital hormone that plays a specific function in the immune system homeostasis,
acting through a nuclear receptor (VDR) expressed in all immune cells. Vitamin D is an
essential element that is known to decrease the risk of developing many chronic illness,
including autoimmune disease(1,2).
Vitamin D, as a steroid hormone, exhibits regulatory effects on growth, proliferation,
apoptosis and function of the immune system cells that are associated with pathophysiology of
SLE. Vitamin D inadequacy is highly prevalent in SLE patients due to avoidance of sunshine,
photoprotection, renal insufficiency and the use of medications such as glucocorticoids,
anticonvulsants, antimalarial and the calcineurine inhibitors, which alter the metabolism of
vitamin D or down regulate the functions of the vitamin D receptor. The association between
vitamin D and systemic lupus erythematosus (SLE) started developing early in the last decade
when the vitamin was related to low bone mass in patients with SLE. It was also related to lack
of sun exposure and to the use of hydroxychloroquine (HCQ) in this patients. Later studies
highlighted the association between SLE and vitamin D(2).

Vitamin D Deficiency and SLE

The association between serum concentrations of vitamin D and the progression and
development of autoimmune disorders has been focused on in several studies. It has been
revealed that disease activity and autoantibody production in SLE cases may be aggravated by
vitamin D insufficiency. Many of the immunomodulatory effects of vitamin D are opposite to
the immunological abnormalities observed with disease activity in SLE patients. So, it can be
concluded that vitamin D deficiency is a risk factor for the onset and development of disease
activity in SLE. Most of vitamin D in the body is produced through the action of ultraviolet B
radiation effects in the skin leading to the generation of cholecalciferol (D3). Cholecalciferol
is converted to 25-hydroxyvitamin D [25(OH)D] in the liver, which is later converted into 1,25-
dihydroxyvitamin in the kidneys. The active form of vitamin D (1,25-dihydroxyvitamin D) has
receptors that are expressed in the immune system, and it potent immunomodulatory that helps
maintain immune homeostasis(2,3).

In recent years there has been an effort to understand possible noncalcemic roles of
vitamin D, including its role in the immune system and in particular, on T cell-mediated
immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and
macrophage populations. However, its highest concentrations is in immature immune cells of
the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds
as selective immunosupressants is illustrated by their ability to either prevent or markedly
suppress animal models of autoimmune disease. Result show that 1,25-dihydroxyvitamin D3
can either prevent or markedly suppress experimental autoimmune disease like
encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, Inflammatory bowel
disease. The vitamin D hormone stimulates transforming growth factor TGFB-1 and
interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity(4).

SLE and Cardiovascular Disease

Patient with systemic lupus erythematosus (SLE) have endothelial dysfunction and
increased risk of cardiovascular disease. Endothelium-dependent dialatation (ED) is abnormal
in patients with SLE, and endothelial repair mechanisms are also impaired.
As shown by evidences, vitamin D deficiency is associated with cardiovascular disease.
Observational studies have revealed a connotation between low 25(OH)D3 level and stroke,
myocardial infarction, hypertensive heart dis- ease, obesity, dyslipidemia, and diabetes
mellitus. and is prevalent in SLE(2,5).

SLE and Renal Disorder

According to the researches there is a connotation between vitamin D deficiency and

SLE renal disorders. I Glomerular involvement causes haematuria, proteinuria and progressive
deterioration of renal function. In a clinical trial conducted by Robinson et al. serum 25(OH)
D levels in patients with SLE were directly connected with serum albumin and inversely
connected with the UP/C ratio and urinary DBP/C. A review of subjects with pediatric SLE
revealed an association between proliferative SLE glomeru- lonephritis and vitamin D
deficiency, and an average 10-ng/ mL difference in serum 25(OH)D levels between subjects
with and without nephritis. Low serum 25(OH)D levels would decrease the amount of
25(OH)D bound to the DBP that is spilled in urine. DBP loss in urine may re ect the magnitude
of proteinuria shown by SLE patients. It has been found that a 20 ng/mL increase in vitamin D
was associated with a 21% decrease in the probability of having a high activity score and a
15% decrease in the possibility of having clinically important proteinuria. Studies on patients
with stage 3 and 4 chronic kidney disease showed that the reduction in proteinuria in the
paricalcitol (a vitamin D compound) treated patients was 3.2 times greater in comparison with
the placebo group. More researches are needed to evaluate the relationship among vitamin D
deficiency in SLE patients and renal diseases. Around 25% of patients with renal impairment
due to SLE will develop glomerulosclerosis, which requires renal replacement therapy(2,6).

SLE and Bone Disease

Improving the intestinal absorption and renal resorption of calcium to increase its
circulating levels that is mediated by the interactions between vitamin D and vitamin D recep-
tors (VDRs) is the main metabolic effect of 1,25(OH)2D. Stimulation of PTH synthesis and
bone resorption can be caused as the result of low levels of vitamin D. Continuance
insuffciency of vitamin D results in rickets and osteomalacia, with skeletal deformities in
children and bone pain and increased risk of fractures in adults(2).

CONCLUSION
Vitamin D is an essential steroid hormone, with well-established effects on mineral
metabolism, skeletal health, and recently established effects on the cardiovascular and immune
systems. Vitamin D deficiency is highly prevalent and evidence is mounting that it contributes
to the morbidity and mortality of multiple chronic diseases, including systemic lupus
erythematosus (SLE). Patients with SLE avoid the sun because of photosensitive rashes and
potential for disease flare. Vitamin D deficiency is common in patient with SLE. Vitamin D
has an immune modulating effect, it is plausible that vitamin D deficiency is not only a risk
factor, but also a consequence of SLE. It is well established that many people have inadequate
levels of 25(OH)D, particularly patients with SLE, who have additional risk factors for
deficiency inherent to SLE. Evidence is accumulating that vitamin D plays a key role in the
pathogenesis and progression of autoimmunity. However, vitamin D supplementation in
patients with SLE is recommended.
REFERENCES
1. C Carvalho*, A Marinho*, B Leal, A Bettencourt, D Boleixa, I Almeida, F Farinha, P
P Costa, C Vasconcelos, B M Silva. Association between vitamin D receptor (VDR)
gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Sage
Journals. 6 Februari:2015.
2. Hassanalilou, T., Khalili, L,. Ghavamzadeh, S,. Shokri, A,. Payahoo, L,. Bishak, K
Yaser,. Autoimmunity Highlights: Role of vitamin D deficiency in systemic lupus
erythematosus incidence and aggravation. (2018) 9:1
3. M Suzan., Attar,. Siddiqui A., Vitamin D Deficiency in Patients with Systemic Lupus
Erythematosus. Oman Medical Journal. (2013) Vol.28, No. 1:42-47
4. Hector, F,. Deluga., Margherita T,. Vitamin D: its role and uses in immunology. The
FASEB JOURNAL. January: 2018 Vol 15:14 pp.2579-2585
5. Reynolds, J,. Ray D., Alexander, M,. Bruce, I,. Role of vitamin D in endothelial
function and endothelial repair in clinically stable systemic lupus erythematosus.
Arthritis Research UK Centre for Epidemiology, University of Manchaster, Machaster
UK. 26 February: 2015.
6. A, Diego,. Sanchez,. Alvarez C., Vasquez., Puerta. Role of TWEAK/Fn14 signalling
pathway in lupus nephritis and other clinical settings. Nefrologia. 2017;37(2):118-125