Discussion
lupus, fatigue, atherosclerotic disease
STILL, DISEASE, RECRUITMENT, LUPUS, VITAMIN D DEFICIENCY, ENDOTHELIAL DYSFUNCTION
In this study on a reasonably large number of patients with SLE, we found that plasma vitamin D level was insufficient in over 41% of individuals. The vitamin D levels depended on the patients’ geographical location and had no relationship to disease activity, autoantibody status or IFN-related proteins. The two study centres Lucknow (26.8467° N, 80.9462° E) and Pondicherry (11.9416° N, 79.8083° E) are located along similar longitude but differ significantly in their distance from the equator (latitudes). The patients recruited at the southern centre had higher vitamin D levels, and the proportion of those who were vitamin D deficient was also substantially lower. This trend was similar in both juvenile and adult patients.A systematic review [Even though we have not compared the vitamin D levels of our patients with those of healthy controls, the available data points to the possibility that patients with lupus may have a similar burden of vitamin D deficiency compared to their matched healthy counterparts in the community. Further, the systematic review from India [The ultraviolet B (UV-B) radiation from sunlight with a wavelength between 290 and 315 nm converts 7-dehydrocholesterol to pre-vitamin D3 in the skin. This pre-vitamin D 3 is rapidly converted to cholecalciferol (vitamin D3) [Another factor that positively correlated with higher vitamin D levels was the age of the patient. It is well known that elderly individuals have lower vitamin D levels [The association studies of vitamin D levels with disease activity in lupus and interferons are variable and have produced contradicting results. While some of the studies have found an association of low vitamin D with specific clinical phenotypes, higher disease activity [Increased interferon (IFN) expression in SLE modestly reflects disease activity measured by SLEDAI. Murine models of lupus have demonstrated association of low vitamin D levels with type-1 IFN gene expression and endothelial dysfunction [In our prospective RCT which included 91 patients followed up to 6 months, the group who received high dose vitamin D had a higher chance of achieving sufficiency in vitamin D levels than those receiving routine dose. However, no difference was observed in terms of improvement in disease activity or prevention of lupus flare. A recently published study showed improvement in disease activity (SLEDAI-2K) and fatigue at 12 months of cholecalciferol supplementation [The strength of our study is the large sample size with details about the usual confounders for vitamin D levels. Moreover, the samples were collected at the beginning of recruitment into the cohort, thus decreasing the effect of background immunosuppressive agents. The sample collection in both the centres was conducted round the year, which negates the effect of seasonal variation in vitamin D levels. However, the effect of drugs administered before their entry into the cohort and the patients’ dietary habits are not accounted for. Still, as the patients had a short duration of symptoms, this factor may not have influenced our results. Another drawback is we have not collected data on vascular health and atherosclerotic disease. This association seems to be strong from recently published studies. Another drawback was the premature termination of the trial due to the COVID pandemic. Larger sample size with a longer duration of follow-up would be required to obtain meaningful data on the effect of vitamin D supplementation on disease activity. With the current study’s data, it would be important to determine the effect of ethnicity, vitamin D receptor polymorphisms and alternate methods of vitamin D administration in lupus.