S Piantoni1, L Andreoli2, M Scarsi2, A Zanola2, F Dall'Ara3, C Pizzorni4, M Cutolo4, P Airò2, A Tincani2. 1. Spedali Civili and University of Brescia, Unit of Rheumatology and Clinical immunology and Department of Clinical and Experimental Sciences, Brescia, Italy University of Pavia, Rheumatology Chair, Pavia, Italy slv.piantoni@gmail.com. 2. Spedali Civili and University of Brescia, Unit of Rheumatology and Clinical immunology and Department of Clinical and Experimental Sciences, Brescia, Italy. 3. Spedali Civili and University of Brescia, Unit of Rheumatology and Clinical immunology and Department of Clinical and Experimental Sciences, Brescia, Italy University of Pavia, Rheumatology Chair, Pavia, Italy. 4. Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy.
Abstract
BACKGROUND:Vitamin D receptor is constitutively expressed on the lymphocyte surface. Recent studies highlight that vitamin D may exert actions on T-cells, inhibiting Th1 and Th17 response and enhancing Th2 and T-regulatory (T-reg) function. METHODS:Thirty-four patients with systemic lupus erythematosus (SLE) were randomly enrolled in a two-year prospective study. In the first year, 16 patients were supplemented with an intensive regimen of cholecalciferol (IR) (300.000 UI of cholecalciferol at baseline and 50.000 UI/monthly as maintenance, 850.000 UI annually), whereas 18 with a standard regimen (SR) (25.000 UI of cholecalciferol monthly, 300.000 UI annually). During the second year, patients were switched to the other arm of treatment. Phenotypic analysis of peripheral T lymphocyte and the quantification of cytokine production from peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry. RESULTS: At baseline, no significant difference between the two groups emerged among main T-cell subtypes. Over two years of treatment, we saw an increase in the number of T-reg cells, in the total amount of CD4+CD45RA+CCR7- T-cells, whereas a significant reduction of CD8+CD28- T-cells was observed. In addition, the analysis of PBMCs from eight patients following the IR showed the reduction of the IFN-γ/IL-4 ratio (p = 0.01) among CD8+ T-cells after 12 months. CONCLUSIONS: After a long-term of monthly treatment with vitamin D in SLE patients, an enhancement of T-reg cells and the production of Th2 cytokines should be expected.
RCT Entities:
BACKGROUND:Vitamin D receptor is constitutively expressed on the lymphocyte surface. Recent studies highlight that vitamin D may exert actions on T-cells, inhibiting Th1 and Th17 response and enhancing Th2 and T-regulatory (T-reg) function. METHODS: Thirty-four patients with systemic lupus erythematosus (SLE) were randomly enrolled in a two-year prospective study. In the first year, 16 patients were supplemented with an intensive regimen of cholecalciferol (IR) (300.000 UI of cholecalciferol at baseline and 50.000 UI/monthly as maintenance, 850.000 UI annually), whereas 18 with a standard regimen (SR) (25.000 UI of cholecalciferol monthly, 300.000 UI annually). During the second year, patients were switched to the other arm of treatment. Phenotypic analysis of peripheral T lymphocyte and the quantification of cytokine production from peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry. RESULTS: At baseline, no significant difference between the two groups emerged among main T-cell subtypes. Over two years of treatment, we saw an increase in the number of T-reg cells, in the total amount of CD4+CD45RA+CCR7- T-cells, whereas a significant reduction of CD8+CD28- T-cells was observed. In addition, the analysis of PBMCs from eight patients following the IR showed the reduction of the IFN-γ/IL-4 ratio (p = 0.01) among CD8+ T-cells after 12 months. CONCLUSIONS: After a long-term of monthly treatment with vitamin D in SLEpatients, an enhancement of T-reg cells and the production of Th2 cytokines should be expected.
Authors: Kendra A Young; Melissa E Munroe; Joel M Guthridge; Diane L Kamen; Timothy B Niewold; Gary S Gilkeson; Michael H Weisman; Mariko L Ishimori; Jennifer Kelly; Patrick M Gaffney; Kathy H Sivils; Rufei Lu; Daniel J Wallace; David R Karp; John B Harley; Judith A James; Jill M Norris Journal: Ann Rheum Dis Date: 2016-06-09 Impact factor: 19.103