• While vitamin D can be effective at preventing the onset of inflammation, it is less effective once inflammatory disease is established because diseases such as rheumatoid arthritis lead to vitamin D insensitivity.
• If vitamin D is to be used in patients with rheumatoid arthritis, clinicians may need to prescribe much higher doses than currently employed or provide a treatment that also corrects the vitamin D insensitivity of immune cells within the joint.
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.
Researchers at the University of Birmingham in the UK used paired peripheral blood and synovial fluid from the inflamed joints of patients with rheumatoid arthritis. The results of their study were published in the Journal of Autoimmunity.
Professor Martin Hewison, of the University of Birmingham’s Institute of Metabolism and Systems Research, said: “Our current understanding of vitamin D and rheumatoid arthritis is based on studies of patient blood which may not truly represent the situation at the site of inflammation—the joints.
“We therefore investigated responses to the active form of vitamin D in immune cells from the inflamed joints of patients with rheumatoid arthritis.
“Compared to blood from the same patients, the inflamed joint immune cells were much less sensitive to active vitamin D.
“This appears to be because immune cells from the joints of rheumatoid arthritis patients are more committed to inflammation, and therefore less likely to change, even though they have all the machinery to respond to vitamin D.”
Implications for physicians
Dr Louisa Jeffery, also of the University of Birmingham, said: “Our research indicates that maintaining sufficient vitamin D may help to prevent the onset of inflammatory diseases like rheumatoid arthritis.
“However, for patients who already have rheumatoid arthritis, simply providing vitamin D might not be enough. Instead much higher doses of vitamin D may be needed, or possibly a new treatment that bypasses or corrects the vitamin D insensitivity of immune cells within the joint.”
Senior author Professor Karim Raza, of the Institution of Inflammation and Ageing at the University of Birmingham, said: “Our findings were unexpected as we initially thought that cells from the inflamed rheumatoid joint would respond just as well to vitamin D as cells from the blood. The fact that they don’t has important implications for how we think about using vitamin D to treat inflammation.
“Unlike previous studies we isolated different immune cell types from the actual site of disease to determine whether specific subsets of immune cells (specific T cell groups) have equal sensitivity to vitamin D.”
The research was funded by Arthritis Research UK and National Institutes of Health USA.
Jeffery LE, Henley P, Marium N, et al. Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint. J Autoimmun. 2017 Oct 21. pii: S0896-8411(17)30420-1. doi: 10.1016/j.jaut.2017.10.001. [Epub ahead of print]