Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency

Figure 6

Biphasic effect of calcitriol on health and autoimmunity. (a) In health, the beneficial effect of calcitriol could be achieved at moderate concentrations presented in the calcidiol sufficiency status. Adequate concentrations of calcidiol and calcitriol (vitamin D sufficiency) allow adequate immunomodulation that improves the immune response and tolerance, favoring polarization towards the tolerogenic Th profiles, reducing the maturation of autoreactive B cells and the antigenic presentation of the dendritic cells, with an increase of IL-10 and TGF-β cytokines. (b) In SLE, lower calcidiol serum levels (vitamin D deficiency) increase the vitamin D hydroxylation efficiency ratio and the extrarenal calcitriol synthesis; this event may occur due to a compensatory mechanism where the immune cell system in a proinflammatory autoimmune context increases the extrarenal hyperactivity of the CYP27B1 enzyme, contributing to an increase in the calcitriol serum concentrations by calcidiol hydroxylation and promotes the exacerbation of the pathological autoimmune response, characterized by a positive feedback loop of the aberrant self-antigenic presentation, the plasma cell differentiation, autoantibody production, autoreactive Th2 polarization, tolerance loss, and damage to tissues.