Vitamin D Tracks Systemic Lupus Erythematosus Activity – MedPage Today

In systemic lupus erythematosus (SLE) low vitamin D status is associated with higher disease activity and erythrocyte sedimentation rate (ESR), while over time, an increase in serum vitamin D levels correlates with reduced SLE activity.

These findings were reported in an Australian study — the first to examine this correlation in the Southern Hemisphere — published online in Lupus Science and Medicine on April 8, 2015.

Following the discovery that vitamin D receptors are expressed by immune cells, vitamin D’s potential role in regulating the immune response has attracted attention, noted researchers led by Kristy Yap, MBBS, of the Centre for Inflammatory Diseases at Monash University, Melbourne.

Deficiency of this vitamin has been associated with several autoimmune diseases including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus, and SLE. A recent study, for example, showed that vitamin D3 inhibits dendritic cell maturation and expression of IFN-induced genes in SLE patients.

During 2007-2013, the Melbourne researchers studied 119 consecutive SLE patients (mean age 42.2) from the Monash Medical Centre Lupus Clinic. Of these, 77.5% were female, 56.3% were white, 37.8% were Asian, and 5.9% were of other or unknown race. With a mean disease duration of 8.7 years and a mean SLEDAI of 5.6, all patients were receiving antimalarial treatment, with 58.8% on glucocorticoids, 33.6% on immunosuppressants, and 14.2% on prednisolone. More than four in 10 (44.5%) were taking vitamin D supplements.

Baseline serum 25-hydroxyvitamin D concentration and disease activity via the SLE Disease Activity Index 2000 SLEDAI-2K) were documented, and adjustments made for the use of glucocorticoids, immunosuppressants, and vitamin D supplements.

At baseline, patients’ mean serum vitamin D was 56.3 mmol/L, and more than a quarter (27.7%) had a deficiency of <40 nmol/L, a finding consistent with reports from other parts of the world.

Patients were also assessed at baseline for inflammatory markers such as ESR, C-reactive protein (CRP), anti-double-stranded DNA antibodies, as well as renal function and complement levels. Bone density of the femoral neck and lumbar spine within 12 months of vitamin D assessment was also measured.

In multiple linear regression analysis, baseline vitamin D level was significantly and inversely correlated with SLEDAI-2K, and with vitamin D supplementation, but not with glucocorticoid use. In a different model that excluded SLEDAI-2K, vitamin D level at baseline was also significantly correlated with ESR (beta=0.3, P=0.01, 95% CI -0.4 to -0.06), even after adjustment for vitamin D supplementation and glucocorticoid use.

The investigators also noted a significant, though weak, inverse correlation between vitamin D level and ESR at baseline (r=0.2, P=0.04), but found no significant correlation between baseline vitamin D and CRP, or with baseline spinal bone density.

As for medication, there was no significant relationship between immunosuppressant use and serum vitamin D level at baseline. As all patients were taking hydroxychloroquine, its relationship to serum vitamin D could not be determined.

No association was found between vitamin D levels and glucocorticoid use, although, according to the authors, it is thought that glucocorticoids may interfere with vitamin D absorption, necessitating higher doses to attain therapeutic levels.

Over 12 months of post-baseline follow-up, a median increase of 25 nmol/L in vitamin D levels was documented, and SLEDAI-2K decreased by an insignificant 2 units. At follow-up, 36.1% in the cohort had low vitamin D and 21.8% had high disease activity (SLEDAI >10).

In regression analysis, a significant association emerged between low vitamin D at a previous time point and a rise of at least 1 unit in SLEDAI-2K at the subsequent time point, with a univariable odds ratio of 3.3 (95% CI 1.5- 7.7, P=0.005). There was also a significant association between low vitamin D at a previous time point and a SLEDAI-2K greater than 10 points at the subsequent time point, with a univariable OR of 3.1 (95% CI 1.4-6.8, P=0.004).

But after adjustment for supplementation, glucocorticoids and immunosuppressant use during the interval, these associations lost significance. This suggests “that vitamin D supplementation and SLE treatment may modify the relationship between serum vitamin D and subsequent disease activity,” the investigators wrote.

“Future studies should include randomized trials which focus on the clinical effect of vitamin D supplementation in SLE and should control for variables that could affect the analysis of benefit,” they concluded.

One study author is a recipient of a David Bickart Clinician Research Fellowship from the University of Melbourne Faculty of Medicine, Dentistry and Health Sciences and holds a National Health and Medical Research Council of Australia Clinical Early Career Research Fellowship.

The authors declared no competing interests.


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