Abstract
Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren’s syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.
Highlights
Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominantly affecting women of child-bearing age at a rate of 20 to 150 cases per 100,000 population [1]
Act1-deficient mice develop a lupus-like disease characterized by hyper-Th17 differentiation and develop a lupus-like disease characterized by hyper-Th17 differentiation
We found no statistical differences in serum IgA, IgE, IgG1, or IgG2b between the groups, a trend for higher Ig levels in the low vitamin D3 group was identified for IgA, IgG1 and IgG2b (Figure 4C–E and data not shown)
Summary
Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominantly affecting women of child-bearing age at a rate of 20 to 150 cases per 100,000 population [1]. While the pathophysiology of SLE is incompletely understood, it is characterized by aberrant T and B cell activity, elevated autoantibody titers, and subsequent organ damage. Autoantibody titers have been shown to increase with disease activity, and newer immunotherapies (e.g., rituximab, belimumab) that target B cells have demonstrated some benefit [2,3]. The Act1-/- mouse is a spontaneous model of lupus and Sjögren’s syndrome, characterized by increased Th17 cells and peripheral B cell expansion. We assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients
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