Involvement of the secosteroid vitamin D in autoimmune rheumatic diseases and COVID-19

Abstract

Evidence supporting the extra-skeletal role of vitamin D in modulating immune responses is centred on the effects of its final metabolite, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 , also known as calcitriol), which is regarded as a true steroid hormone. 1,25(OH) 2 D 3 , the active form of vitamin D, can modulate the innate immune system in response to invading pathogens, downregulate inflammatory responses and support the adaptive arm of the immune system. Serum concentrations of its inactive precursor 25-hydroxyvitamin D 3 (25(OH)D 3 , also known as calcidiol) fluctuate seasonally (being lowest in winter) and correlate negatively with the activation of the immune system as well as with the incidence and severity of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Thus, a low serum concentration of 25(OH)D 3 is considered to be a risk factor for autoimmune rheumatic diseases and vitamin D 3 supplementation seems to improve the prognosis; moreover, long-term vitamin D 3 supplementation seems to reduce their incidence (i.e. rheumatoid arthritis). In the setting of COVID-19, 1,25(OH) 2 D 3 seems to downregulate the early viral phase (SARS-CoV-2 infection), by enhancing innate antiviral effector mechanisms, as well as the later cytokine-mediated hyperinflammatory phase. This Review provides an update of the latest scientific and clinical evidence concerning vitamin D and immune response in autoimmune rheumatic diseases and COVID-19, which justify the need for monitoring of serum 25(OH)D 3 concentrations and for appropriate supplementation following clinical trial-based approaches.

The 2023’s Growing Evidence Confirming the Relationship between Vitamin D and Autoimmune Diseases

“…Moreover, in two different Iranian and Saudi Arabia cohorts (92 and 102 RA patients, respectively), hypovitaminosis D was significantly correlated with RA disease activity scores (DAS), like DAS28-CRP [11] or DAS28-ESR [12], as reported in previous studies [1].…”

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE

“…Vitamin D, as a secosteroid and a strong immunosuppressant, plays important roles in the autoimmune diseases. 43 Several studies have shown that VitD3 and its analogues inhibit the maturation of mDCs and maintained its immature phenotype, which can ameliorate autoimmune inflammation and induce immune tolerance. 18,44,45…”

Understanding the Immune-Endocrine Effects of Vitamin D in SARS-CoV-2 Infection: A Role in Protecting against Neurodamage

“…Vitamin D 3 is a fat-soluble steroid hormone with pleiotropic biologic effects [ 1 ]. It is derived from both food and from the physiological photoconversion of cutaneous 7-dehydrocholesterol into pre-vitamin D 3 and then into cholecalciferol, following exposure to UV-B solar rays.…”

“…Schematically, when hydroxylation in position 1 occurs in the kidney, calcitriol exerts endocrine rapid non-genomic effects on target cells (gut epithelial cells, osteoblasts, osteoclasts, parathyroid cells, tubular renal cells), regulating calcium-phosphorus homeostasis (shown in Fig. 1 ) [ 1 ]. On the other hand, when hydroxylation in position 1 occurs in immune cells, calcitriol exerts paracrine/autocrine slower genomic effects on immune cells themselves, downregulating autoimmune/inflammatory processes (shown in Fig.…”