Background/Purpose: Exposure of normal PBMCs to1,25 OH vitamin D reverses the stimulatory effects of activating SLE sera on the interferon signature.  Given that IFN is made by activated plasmacytoid dendritic cells (pDCs), vitamin D maintains pDC quiescence, and vitamin D deficiency has a high prevalence in SLE, we investigated the effect of vitamin D supplementation on the IFN signature in SLE patients. Secondary aims included determination of the effect of vitamin D on disease activity and the safety/tolerability of vitamin D in deficient SLE patients.

Methods: 57 anti-DNA antibody positive SLE patients from 8 centers with stable, inactive (SLEDAI ≤4) disease, serum 25-OH vitamin D ≤20ng/ml and an IFN signature were randomized (1:1:1) into a 12 week double-blind placebo controlled trial of daily oral vitamin D3. A IFN signature was defined to be present if expression of 1 of 3 IFN responsive genes (Mx1, Ifit1, or Ifi44) determined using RT-PCR of whole blood mRNA was expressed at a level ≥ 4 SD above the mean of normal controls, or if 2 of the 3 genes were expressed > 2 SD above the mean of normal controls. Immunosuppressive medications were required to be stable at baseline with no expectation of change during the 12 week treatment period. Subjects received 0, 2000 or 4000 IU vitamin D3 daily.  A IFN signature response was defined as a 50% reduction in the expression of 1 gene or a 25% decrease in 2 genes compared to baseline provided that expression of the remaining genes did not increase >25%.  Measures of disease activity, safety, tolerability and endocrine effects (PTH, urinary calcium/creatinine) were collected.

Results: Baseline characteristics of the 3 treatment groups were similar.  Mean (SD) 25 OH D levels (ng/mL) were comparable across treatment groups at entry:  14.5 (4.65), 12.6 (3.76) and 15.3 (3.08) for placebo, low dose and high dose, respectively.  No subjects receiving placebo achieved levels associated with endocrine repletion (25 OH D ≥ 30ng/ml) while 11 of 18 subjects receiving 4000 IU daily and 5 of 15 receiving 2000 IU daily exceeded that threshold. The percent of subjects with an IFN signature response was not significantly different among treatment groups at Week 12 (36.8, 23.5, 27.8; placebo, 2000 IU/day dose, 4000 IU/day dose respectively).  At Week 12, 36% of deficient subjects and 31% of subjects with 25 OH D values ≥ 30 ng/ mL had an IFN signature response (NS). Furthermore, there was no significant difference in 25 OH D levels between subjects with and without an IFN signature response. Results did not differ significantly whether analyzed per protocol or by intent-to-treat. Vitamin D3 was well tolerated with no safety concerns and no treatment related serious adverse events.

Conclusion: These results suggest that vitamin D3 at doses up to 4000 IU daily was safe and well-tolerated in SLE patients.  However, daily doses of vitamin D3 for 12 weeks failed to diminish the IFN signature in vitamin D deficient SLE patients, although repletion of 25 OH D to levels associated with bone health (≥ 30ng/ml) was only achieved in a minority of trial participants. Higher levels of 25 OH D sustained for longer duration may be required for affecting the anticipated immunological outcomes.

Sponsored by NIAID Autoimmunity Centers of Excellence: NCT00710021

---

« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-placebo-controlled-trial-of-the-effect-of-vitamin-d3-on-the-interferon-signature-in-patients-with-systemic-lupus-erythematosus/