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+CD25(bright)Foxp3-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.
Zold
Eva
E
Division of Clinical Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Szodoray
Peter
P
Nakken
Britt
B
Barath
Sandor
S
Kappelmayer
Janos
J
Csathy
Laszlo
L
Hajas
Agota
A
Sipka
Sandor
S
Gyimesi
Edit
E
Gaal
Janos
J
Barta
Zsolt
Z
Hallay
Judit
J
Szegedi
Gyula
G
Bodolay
Edit
E
D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002675:Child, Preschool; D003240:Connective Tissue Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage*; D007154:Immune System Diseases / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D007223:Infant; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology*; D008297:Male; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy* / Q000276:immunology
D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D020381:Interleukin-17; D007371:Interferon-gamma; C008088:alfacalcidol