577 - Restoration of Regulatory T Cells-Th17 Cells Balance in Systemic Lupus Erythematosus Through Vitamin D Supplementation

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Benjamin Terrier1, Yoland Schoindre2, Guillaume Geri3, David Saadoun4, Kubéraka Mariampillai5, Michelle Rosenzwajg6, David Klatzmann6, Jean-Charles Piette3, Patrice Cacoub3 and Nathalie Costedoat-Chalumeau3, 1Pitié-Salpêtrière Hospital, Paris, France, 2Foch Hospital, Suresnes, France, 3CHU Pitié-Salpêtrière, Paris, France, 4Department of Internal Medicine and Laboratory I3 “Immunology, Immunopathology, Immunotherapy”, UMR CNRS 7211, INSERM U959, Groupe Hospitalier Pitié-Salpetrière, Université Pierre et Marie Curie, Paris 6, Paris, France, Paris, France, 5Pitié-Salpétrière Hospital, Paris, France, 6Laboratory I3 “Immunology, Immunopathology, Immunotherapy”, UMR CNRS 7211, INSERM U959, Paris, France
Presentation Number: 577

Background/Purpose: Systemic lupus erythematosus (SLE) is associated with perturbations in regulatory T cells (Tregs), T helper lymphocytes producing interleukin (IL)-17 (Th17 cells) and B cells. Immunomodulatory effects of vitamin D were recently described in vitro, notably the expansion of Tregs able to suppress inflammatory responses and the decrease of Th17 cells. Objective. To evaluate tolerance and immunologic and clinical effects of vitamin D supplementation in SLE.

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. 

Keywords: B cells, interleukins (IL), regulatory cells, systemic lupus erythematosus (SLE) and vitamins

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.