Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3 + /IL-17A ratio and clinical course in system

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THERAPEUTIC ASPECTS IN AUTOIMMUNITY

Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3+/IL-17A ratio and clinical course in systemic lupus erythematosus patients: a study in a Portuguese cohort Anto´nio Marinho1,2 • Cla´udia Carvalho1 • Daniela Boleixa1 • Andreia Bettencourt1 Ba´rbara Leal1 • Judite Guimara˜es1,3 • Esmeralda Neves3 • Jose´ Carlos Oliveira4 • Isabel Almeida1,2 • Fa´tima Farinha1,2 • Paulo P. Costa1 • Carlos Vasconcelos1,2 • Berta M. Silva1



Anto´nio Marinho

Ó Springer Science+Business Media New York 2016

Abstract Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi-organ inflammation, linked to loss of immune tolerance to self-antigens and the production of a diversity of autoantibodies, with a negative impact on the patients’ quality of life. Regulatory T cells have been reported as deficient in number and function in SLE patients. However, some authors also described an enrichment of this cell type. The hypothesis that certain forms of autoimmunity may result from a conversion of Treg cells into a Th17 cell phenotype has been suggested by some studies. In fact, in SLE patients’ sera, the IL-17 levels were observed as abnormally high when compared with healthy individuals. Environmental factors, such as vitamin D, that is considered a potential antiinflammatory agent, combined with genetic and hormonal characteristics have been associated with SLE phenotype and with disease progression. The aim of this study was to evaluate the effect of vitamin D supplementation on FoxP3 expression and IL-17A-producing T cells, through FoxP3?/IL-17A ratio. Additionally, disease evolution, serum vitamin D levels, serum autoantibodies levels and calcium metabolism (to assure safety) were also studied. We assessed 24 phenotypically well-characterized SLE patients. All patients were screened before vitamin D supplementation and 3 and 6 months after the beginning of this treatment. Peripheral blood lymphocyte’s subsets were analysed by flow cytometry. Serum 25(OH)D levels significantly increased under vitamin D supplementation (p = 0.001). The FoxP3?/IL-17A ratio in SLE patients after 6 months of vitamin D supplementation was higher than that in the baseline (p \ 0.001). In conclusion, this study demonstrated that vitamin D supplementation provided favourable, immunological and clinical impact on SLE. Keywords SLE  Vitamin D  FoxP3 T cells  IL-17A T cells

Introduction

& Anto´nio Marinho [email protected] 1

UMIB, Instituto de Cieˆncias Biome´dicas de Abel Salazar (ICBAS), UPorto, Porto, Portugal

2

Unidade Imunologia Clı´nica, Centro Hospitalar do Porto, Hospital Santo Anto´nio, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal

3

Servic¸o de Imunologia, Centro Hospitalar do Porto, Hospital Santo Anto´nio, Porto, Portugal

4

Departamento de Patologia Clı´nica, Centro Hospitalar do Porto, Hospital Santo Anto´nio, Porto, Portugal

Systemic lupus erythematosus (SLE or lupus) is a systemic autoimmune disease with multi-organ inflammation [1, 2], linked t