Aims: 

Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25^brightFoxp3-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-g expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells.

Methods: 

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 mg/day, 7 patients with 1.0 mg/day, and 7 patients with 1.5 mg/day alfacalcidol treatment during 5 weeks. Plasma levels of 25(OH)D were assessed by HPLC method. Flow cytometry was used for the quantification of nTreg and IL-17 expressing Th17 cells. The plasma concentrations of cytokines, interleukin (IL)-12, IFN-gamma, IL-23, IL-17, IL-6 and IL-10 were measured by ELISA.

Results: 

Our results indicated that 1.0 mg/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, decrease both Th1 (IL-12 and IFN-gamma) and Th17 related (IL-23, IL-17, IL-6) cytokine levels repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells in UCTD patients. 1.5 mg daily dose alfacalcidol was not more effective than the 1.0 mg/day treatment.

Conclusion: 

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.