Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease

Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25brightFoxp3-natural regulatory T cells–nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-γ expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (< 30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 μg/day, 7 patients with 1.0 μg/day, and 7 patients with 1.5 μg/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 μg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25− cells. 1.5 μg daily dose alfacalcidol was not more effective than the 1.0 μg/day treatment.In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease.