Vitamin D and Lupus

The effects of vitamin D on the immune system of people with lupus has been examined in a new study for the first time. This study was reported this week at the American College of Rheumatology Annual Scientific Meeting in Chicago. Systemic lupus erythematosus, also called SLE or lupus, is a chronic inflammatory disease that can affect the skin, joints, kidneys, lungs, nervous system, and/or other organs of the body. The most common symptoms include skin rashes and arthritis, often accompanied by fatigue and fever. Lupus occurs mostly in women, typically developing in individuals in their twenties and thirties - prime child-bearing age.

There is a connection between lupus and the disturbance of regulatory T cells (which play an important role in maintaining a healthy immune system), T helper lymphocytes (white blood cells that assist other white blood cells in the immune system), and B cells (which make antibodies that fight off attacks on the immune system). Vitamin D has been shown to affect the numbers and function of many of these immune cells. Because of this connection, researchers - led by Benjamin Terrier, MD; Patrice Cacoub, MD, PhD; and Nathalie Costedoat-Chalumeau, MD,PhD; from the Internal Medicine Department of the Pitié-Salpétrière Hospital in Paris, France - studied 24 people with lupus to determine their vitamin D status and to determine whether vitamin D supplementation would be well tolerated and potentially beneficial to their immune systems. Only patients with no or mild lupus activity were included in this study.

All of the participants in the study were taking a stable dose of prednisone and/or immunosuppressive drugs. Each participant with vitamin D deficiency received vitamin D supplementation (100,000 IU of cholecalciferol) each week for four weeks followed by the same amount each month for six months. Researchers evaluated each participant at the beginning of the study, at two months, and again at six months to see how well they were tolerating the supplementation and how it was affecting their immune systems. Researchers also analyzed the blood lymphocytes of each participant at the three time-points to monitor the evolution of regulatory T cells, T helper lymphocytes and B cells under vitamin D therapy.

Among the 24 patients in the study, 20 (who were around the age of 30) had low levels of vitamin D and received supplementation. The researchers noted the supplementation was safe, and the participants did not develop too much calcium in their blood or calcium deposits (such as kidney stones).

Serum 25(OH)D levels dramatically increased with vitamin D supplementation - reaching normal values at two months and six months. The clinical activity of lupus did not change significantly, and none of the patients showed a flare of the disease or required an increase in corticosteroids or immunosuppressive drugs. However, the levels of anti-DNA antibodies, which are abnormal and pathogenic antibodies produced by B cells, decreased at two months and six months.

The number of regulatory T cells increased with vitamin D supplementation at both two and six months, with a similar trend for both naïve and activated memory regulatory T cells, which represent two subsets of regulatory T cells. This increase of regulatory T cells was also associated with an increased expression of molecules associated with their suppressive function (i.e., GITR and LAP).

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A decrease in T helper lymphocytes, previously shown to be increased in lupus, was noted after two months of vitamin D supplementation. Finally, researchers observed a decrease in memory B cells (which produce antibodies) at two months and in activated CD8+ T cells (which may contribute to the disease process in lupus) at six months. Taken together, these results provide evidence of normalization of abnormal lymphocyte numbers in these patients.

"This preliminary study provides encouraging results and suggests the beneficial role of vitamin D supplementation in patients with SLE, with an increase of regulatory T cells and a decrease of memory B cells and effector T cells," explains Dr. Terrier. "However, these findings need to be confirmed in large randomized controlled trials."

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The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on Twitter by using the official hashtag: #ACR2011.





Editor’’s Notes: Benjamin Terrier, MD, will present this research during the ACR Annual Scientific Meeting at the McCormick Place Convention Center from 9:00 - 11:00 AM on Sunday, November 6 in Hall F2. Dr. Terrier will be available for media questions and briefing at 8:30 AM on Tuesday, November 8 in the on-site press conference room, W 175C.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’’s Simple Tasks campaign, which highlights how rheumatic diseases strike women disproportionately and in the prime of their lives.

Presentation Number: 577

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

Benjamin Terrier (Pitié-Salpêtrière Hospital, Paris, France)
Yoland Schoindre (Foch Hospital, Suresnes, France)
Guillaume Geri (CHU Pitié-Salpêtrière, Paris, France)
David Saadoun (Department 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)
Kubéraka Mariampillai (Pitié-Salpétrière Hospital, Paris, France)
Michelle Rosenzwajg (Laboratory I3 Immunology, Immunopathology, Immunotherapy, UMR CNRS 7211, INSERM U959, Paris, France)
David Klatzmann (Laboratory I3 Immunology, Immunopathology, Immunotherapy, UMR CNRS 7211, INSERM U959, Paris, France)
Jean-Charles Piette (CHU Pitié-Salpêtrière, Paris, France)
Patrice Cacoub (CHU Pitié-Salpêtrière, Paris, France)
Nathalie Costedoat-Chalumeau (CHU Pitié-Salpêtrière, Paris, France)

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.

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.




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