Tuesday, 20 Mar 2018

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Vitamin D Insensitivity in the Rheumatoid Joint

Researchers from the University of Birmingham have shown that while Vitamin D may be effective at preventing the onset of inflammation, it is less effective once inflammatory disease is established - largely because, once established, rheumatoid arthritis leads to vitamin D insensitivity. (Citation source https://buff.ly/2iGHYmI)

Another key finding of the research was that the impact of vitamin D on inflammatory disease cannot be predicted using cells from healthy individuals or even from the blood of patients with inflammation as cells from the diseased tissue behave in a very different way.

In addition to its well-established actions on the skeleton, vitamin D is a potent modulator of the immune system. In particular, vitamin D can suppress inflammation in autoimmune diseases such as rheumatoid arthritis. Patients with rheumatoid arthritis are frequently vitamin D deficient and may receive vitamin D supplementation.

1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects, including suppression of IL-17 + and IFNγ+ T cells. They studied cells from paired peripheral blood and synovial fluid (SF) samples patients with active RA. Specifically they sought to assess cellular responses to the active form of vitamin D.

Overall theyfound that cells taken from the joints of RA patients were much less sensitive to active vitamin D. 1,25(OH)2D3 had significantly less suppressive effect on Th17 cells (IL-17+IFNγ-) and Th17.1 cells (IL-17+IFNγ+) from SF compared to those from blood, and had no effect on SF CD4+ or CD8+ IFNγ+ T cell frequencies. Memory T cells (CD45RO+) predominate in SF, and 1,25(OH)2D3 had less effect on memory T cells relative to naïve (CD45RA+) T cells.

Thus the potential anti-inflammatory effects of vitamin D in active RA are impaired because of reduced effects on phenotype-committed, inflammatory memory T cells that are enriched in SF. (Such cells are already overcommitted to inflammation)

Researchers postulated that much higher doses of vitamin D may be needed to overcome the vitamin D insensitivity within the joint. Restoration of 1,25(OH)2D3 responses in memory T cells, by whatever means,  may provide a new strategy for treatment of inflammatory diseases such as RA. 

The author has no conflicts of interest to disclose related to this subject

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