Method: In this monocenter prospective study, we measured vitamin D level in SLE patients (according to the revised ACR criteria). Patients with hypovitaminosis D (< 30 ng/mL) and stable dosage of prednisone and/or immunosuppressant agents received vitamin D supplementation: 100 000 UI of cholecalciferol per week for 4 weeks, followed by 100 000 UI per month for 6 months. Patients were screened at day 0 (D0) and at month 2 (M2) and 6 (M6) after the beginning of vitamin D supplementation. The end points were tolerance, immunologic effects and clinical efficacy.
Result: Among 24 patients, 20 (20 women, age 31±8 years) had low vitamin D levels and received vitamin D supplementation. Treatment was safe with no hypercalcemia or lithiasis. Serum 25(OH)D levels dramatically increased from 18.7±6.7 at D0 to 51.4±14.1 (p<0.001) at M2 and 41.5±10.1 ng/mL (p<0.001) at M6. Disease activity assessed by the SLEDAI was 2.9±2.5 at D0, 2.6±2.5 at M2 (p=0.67) and 1.9±1.8 at M6 (p=0.16). Anti-DNA levels decreased from 177±63 at D0 to 124±67 at M2 (p<0.05) and 103±36 UI/mL at M6 (p<0.01). The percentage of Tregs (CD4+CD25hiCD127-FoxP3+) increased under vitamin D supplementation (3.5±1.2% at D0 to 4.6±1.3% at M2 and 4.3±1.4% at M6, p<0.001 and p<0.01, respectively) with a similar trend between naïve and activated memory Tregs. This was associated with an increased expression of molecules associated with suppression of Tregs (i.e. GITR and LAP). A decrease in Th17 (2.0±1.1% at D0 to 1.6±0.9% at M2 and 2.0±1.3% at M6, p<0.01 and p=0.81, respectively) and Th1 cells (16.9±6.7% at D0 to 11.0±5.1% at M2 and 13.6±6.5% at M6, p<0.01 and p<0.05, respectively) was observed mainly after 2 months of vitamin D supplementation. We also observed a decrease in class-switched memory B cells (28.1±14.5% at D0 to 24.7±12.6% at M2 and 27.6±14.6% at M6, p<0.05 and p=0.65, respectively) and HLA-DR+ CD8+ T cells (46.0±15.0% at D0 to 40.8±16.8% at M2 and 36.1±18.2% at M6, p=0.12 and p<0.001, respectively).
Conclusion: This is the first study to report the immunologic effects of vitamin D supplementation in vivo during SLE. Vitamin D modulates the Tregs-Th17 balance by increasing Tregs and decreasing the Th17 cells, and decreases Th1 cells and memory B cells. This study suggests the beneficial role of vitamin D in SLE which needs to be confirmed in randomized controlled trials.
Disclosure: B. Terrier, None; Y. Schoindre, None; G. Geri, None; D. Saadoun, None; K. Mariampillai, None; M. Rosenzwajg, None; D. Klatzmann, None; J. C. Piette, None; P. Cacoub, None; N. Costedoat-Chalumeau, None.