The Impact of Vitamin D on the Immunopathophysiology, Disease Activity, and Extra-Musculoskeletal Manifestations of Systemic Lupus Erythematosus

Abstract

Over the past two decades it has been increasingly recognized that vitamin D, aside from its crucial involvement in calcium and phosphate homeostasis and the dynamics of the musculoskeletal system, exerts its influential impact on the immune system. The mechanistic roles that vitamin D plays regarding immune activation for combating infection, as well as pathologically and mediating autoimmune conditions, have been progressively unraveled. In vitro and in vivo models have demonstrated that the action of vitamin D on various immunocytes is not unidirectional. Rather, how vitamin D affects immunocyte functions depends on the context of the immune response, in the way that its suppressive or stimulatory action offers physiologically appropriate and immunologically advantageous outcomes. In this review, the relationship between various aspects of vitamin D, starting from its adequacy in circulation to its immunological functions, as well as its autoimmune conditions, in particular systemic lupus erythematosus (SLE), a prototype autoimmune condition characterized by immune-complex mediated inflammation, will be discussed. Concurring with other groups of investigators, our group found that vitamin D deficiency is highly prevalent in patients with SLE. Furthermore, the circulating vitamin D levels appear to be correlated with a higher disease activity of SLE as well as extra-musculoskeletal complications of SLE such as fatigue, cardiovascular risk, and cognitive impairment.

Vitamin D and Human Health

“…For instance, it was recently suggested that vitamin D could be useful in the prevention and treatment of autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus, rheumatoid arthritis, or systemic lupus erythematous (SLR). The consequence of vitamin D deficiency in the lupus development and progression was reviewed by Mak [12]. Strikingly, exposure to UV light is a major contributor to SLR flare up, thus the sun avoidance behavior only aggravates vitamin D deficiency in patients with lupus.…”

“…Strikingly, exposure to UV light is a major contributor to SLR flare up, thus the sun avoidance behavior only aggravates vitamin D deficiency in patients with lupus. On the other hand, a few recent clinical studies suggested not only a correlation of vitamin D deficiency with the severity of lupus, but also that proper supplementation may inhibit the production of autoantibodies, decrease the Th1/Th17 and memory B cells fractions, and reduce fatigue [12]. Furthermore, an increased activity of the immune system, including production of specific antibodies, is also the most important cause of graft-versus-host disease in recipients of allogeneic hematopoietic stem cell transplantation.…”

Association of serum vitamin D levels with chronic disease and mortality

“…In this study we reported an association between chronic disease and low 25-(OH)-D3 levels, specifically regarding metabolic and autoimmune levels. Moreover, we had no information related to antibody titers and severity of disease in the case of autoimmune disorders; subsequently, it would be interesting to find out if higher disease activity is correlated with 25-(OH)-D3 levels as implied by previous studies (40). In addition, only including patients already diagnosed with a chronic disease constitutes a relevant bias, as vitamin D levels could be lower due to the fact that the subjects have a health condition but not conversely.…”

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

“…Furthermore, vitamin D exerts a protective role in podocyte injury induced by autoantibodies from patients with nephritis [99]. Lower vitamin D levels in the bloodstream appear to be associated with worse disease activity, as well as with extra-musculoskeletal complications such as fatigue [100], cardiovascular risk [101], and cognitive impairment [102,103]. In addition, a recent longitudinal cohort analysis showed that vitamin D deficiency was associated with more active disease at baseline and over time, as well as a trend toward more severe lupus flares [104].…”