VITAMIN D EFFECT ON T LYMPHOCYTES AND OSTEOCLASTOGENESIS IN RHEUMAOID ARTHRITIS Abstract (5000) Rheumatoid arthritis (RA) is an immune-mediated disease characterized by articular inflammation and subsequent tissue damage, which lead to severe disability and increased mortality. RA is characterized b

Abstract

5000) Rheumatoid arthritis (RA) is an immune-mediated disease characterized by articular inflammation and subsequent tissue damage, which lead to severe disability and increased mortality. RA is characterized by invasive synovial hyperplasia leading to progressive joint destruction. Radiographic studies have shown that bone erosion in RA begins at an early stage of the disease and gradually or rapidly exacerbates. Bone erosion results in severe deformities of the affected joints and impairs normal activity and quality of life. The immune alterations in RA are complex and not completely understood, it is generally accepted that T helper (Th) 1 cells are the main responsible for the immune alteration together with an increase in Th17 and a decrease in T regulatory cells (T reg). Furthermore there is an increase in osteoclasts formation and activity both at the level of the inflamed joint both at systemic level. Recent in vitro and in vivo data suggest that 1,25Dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D3, is exerts pleiotropic effects on the growth and differentiation of many cell types, and displays exquisite immunoregulatory properties. It has been suggested that [1,25(OH)2D3] exerts direct modulatory effects on T-cell and B-cell function and on dendritic cells (DCs), thereby promoting tolerogenic properties that favor the induction of regulatory, rather than effector, T cells. The role of vitamin D in the pathogenesis and in the treatment of RA is still controversial. Some studies suggested a role for low vitamin D intake in the pathogenesis of RA and others also suggest a potential therapeutic effect for vitamin D in RA. The aim of this study are to: 1explore the role of vitamin D in the pathogenesis of early RA 2evaluate the role of vitamin D as immunomodulator in early RA 3evaluate the effect of vitamin D on osteoclastogenesis in early RA 4evaluate the clinical effect of vitamin D in early RA In vitro experiments In order to test if T cells from RA patients are equally responsive to vitamin D as respect to healthy age and sex matched controls we will measure vitamin D receptor (VDR) by real time PCR and western blot in fractoned (T cells, B cells and monocytes) and unfractioned PBMC from RA patients and controls. To evaluate if PBMC from RA patients and healthy donors has the same ability to produce and /or inactivate vitamin D we will explore the ability of fractioned and unfractioned PBMC from RA patients and healthy donors to hydroxilate 25 OH vitamin D in position 1 to obtain the active metabolite 1,25 OH vitamin D, and the ability of these cells to inactivate vitamin D through hydroxylation in position 24. The metabolites will be measure after a short incubation with 25 OH vitamin d and 1-25OH vitamin D by HPLC.