**3. Vitamin D and autoimmune diseases**

There are several animal models of autoimmunity, in which disease could either be prevented or ameliorated with the administration of either 1,25(OH)2D3 or one of its analogues. These animal models are models of autoimmune encephalomyelitis, collagen-induced arthritis, type 1 diabetes mellitus, inflammatory bowel disease, autoimmune uveitis, and lupus [44, 56, 62–76]. These studies show that treatment with active vitamin D is effective in modulating immune function and ameliorating autoimmune disease. Vitamin D deficiency is a risk factor for the development of some autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), diabetes mellitus type 1, multiples sclerosis, inflammatory bowel disease, and Hashimoto's thyroiditis [49, 69, 74, 77–85] (**Figure 2**). Additionally, vitamin D deficiency has been observed in patients with systemic sclerosis [86].

#### **3.1 Vitamin D deficiency and rheumatoid arthritis**

A meta-analysis showed that low vitamin D intake is associated with the development of RA [87]. Thereafter, several studies performed in various areas all over the world showed that vitamin D deficiency is observed in patients with RA and that vitamin D deficiency is associated with disease activity [78, 82, 83, 88–97]. A meta-analysis of the good quality studies performed regarding the association between vitamin D deficiency and RA showed that vitamin D deficiency is observed in RA patients significantly more than in a control group and that vitamin D levels are inversely correlated with disease activity, meaning that low vitamin D levels are associated with high-disease activity [98]. Moreover, an

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reverse diabetes mellitus type 1.

**3.4 Vitamin D deficiency and multiple sclerosis**

*Vitamin D and Autoimmune Diseases*

*DOI: http://dx.doi.org/10.5772/intechopen.89707*

inhibitors in RA treatment [77, 101].

activity [108].

association has been shown between VDR polymorphism and RA. Specifically, the Fokl F allele of the VDR may be a risk factor for the development of RA [99]. Further studies are needed to unravel the exact association between vitamin D deficiency and RA and to determine the best method of vitamin D supplementation and whether it may be used for the prevention of RA or for the best management of the disease [77, 100]. In addition, it has been proposed that vitamin D may contribute to the management of pain in RA and may be used along with TNF-α

In SLE, the inflammatory milieu drives the development of T cells into proinflammatory pathways, defective function of Tregs, and survival and activation of B cells, which produce autoantibodies [78, 81]. Patients with systemic lupus erythematosus have lower 25(OH)D3 levels compared to controls, suggesting that vitamin D deficiency may be a risk factor for SLE [81, 84, 102–107]. The majority of studies have also found higher SLE disease activity associated with lower levels of 25(OH)D3 [84, 103]. As patients with SLE have often photosensitivity and are advised to avoid direct sun exposure, detecting vitamin D deficiency and replacing 25(OH)D3 with oral supplementation is critical and may impact disease

Type 1 diabetes mellitus is one of the most prevalent chronic diseases with onset in childhood and is the result of immune-mediated destruction of pancreatic insulin producing β cells. There appears to be a geographic variation in incidence following a gradient in latitude, which is the inverse of the global distribution of ultraviolet B irradiation, critical for the production of vitamin D within the skin [109]. Studies have shown higher incidence of vitamin D deficiency in patients with type 1 diabetes [110–113]. One environmental factor thought to be protective against the development of type 1 diabetes mellitus is early supplementation with vitamin D [114]. A number of large case control studies showed that the risk of type 1 diabetes mellitus was significantly reduced in infants who were supplemented with vitamin D compared to those who were not supplemented [115–117]. Additionally, a lower incidence of type 1 diabetes was observed in infants born to mothers who were administered cod liver oil during pregnancy [118]. A birth cohort study in Finland, now more than 50 years ago, evaluated the effects of vitamin D supplementation on rickets and the development of type 1 diabetes mellitus [85]. All women due to give birth in 1966 were enrolled. There was an 80% reduction in the risk for type 1 diabetes mellitus in children having received >2000 IU vitamin D/day compared to those receiving less or not receiving supplementation with vitamin D. Evidence from both human and animal studies shows that vitamin D may be protective as far as the development of type 1 diabetes mellitus is concerned [68, 71, 76]. Thus, the administration of vitamin D may prevent diabetes mellitus type 1; however, once the destruction of pancreatic beta cells has taken place, it will not act therapeutically to

Multiple sclerosis is characterized by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system, which can result in disability. Epidemiological studies have suggested that vitamin D insufficiency

**3.2 Vitamin D deficiency and systemic lupus erythematosus**

**3.3 Vitamin D deficiency and type 1 diabetes mellitus**

**Figure 2.** *Autoimmune diseases related to vitamin D deficiency.*

*Vitamin D and Autoimmune Diseases DOI: http://dx.doi.org/10.5772/intechopen.89707*

*Vitamin D Deficiency*

systemic sclerosis [86].

Vitamin D appears to have a direct effect on B cells and inhibits immunoglobulin production [57]. Additionally, differentiation of B cells is interrupted when exposed to 1,25(OH)2D3. 1,25(OH)2D3 also has effects on dendritic cells. Dendritic cells have important functions in maintaining both protective immunity and self-tolerance [58, 59]. Physiologic levels of 1,25(OH)2D3 inhibit maturation of dendritic cells and maintain an immature and tolerogenic phenotype with inhibition of activation markers such as MHC class II, CD40, and others and upregulation of inhibitory molecules [60, 61]. Thus, it appears that the maturational state of dendritic cells can be modulated by 1,25(OH)2D3, making it possible that the vitamin D status of an

There are several animal models of autoimmunity, in which disease could either be prevented or ameliorated with the administration of either 1,25(OH)2D3 or one of its analogues. These animal models are models of autoimmune encephalomyelitis, collagen-induced arthritis, type 1 diabetes mellitus, inflammatory bowel disease, autoimmune uveitis, and lupus [44, 56, 62–76]. These studies show that treatment with active vitamin D is effective in modulating immune function and ameliorating autoimmune disease. Vitamin D deficiency is a risk factor for the development of some autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), diabetes mellitus type 1, multiples sclerosis, inflammatory bowel disease, and Hashimoto's thyroiditis [49, 69, 74, 77–85] (**Figure 2**). Additionally, vitamin D deficiency has been observed in patients with

A meta-analysis showed that low vitamin D intake is associated with the development of RA [87]. Thereafter, several studies performed in various areas all over the world showed that vitamin D deficiency is observed in patients with RA and that vitamin D deficiency is associated with disease activity [78, 82, 83, 88–97]. A meta-analysis of the good quality studies performed regarding the association between vitamin D deficiency and RA showed that vitamin D deficiency is observed in RA patients significantly more than in a control group and that vitamin D levels are inversely correlated with disease activity, meaning that low vitamin D levels are associated with high-disease activity [98]. Moreover, an

individual is likely to have important immunologic consequences.

**3. Vitamin D and autoimmune diseases**

**3.1 Vitamin D deficiency and rheumatoid arthritis**

**232**

**Figure 2.**

*Autoimmune diseases related to vitamin D deficiency.*

association has been shown between VDR polymorphism and RA. Specifically, the Fokl F allele of the VDR may be a risk factor for the development of RA [99]. Further studies are needed to unravel the exact association between vitamin D deficiency and RA and to determine the best method of vitamin D supplementation and whether it may be used for the prevention of RA or for the best management of the disease [77, 100]. In addition, it has been proposed that vitamin D may contribute to the management of pain in RA and may be used along with TNF-α inhibitors in RA treatment [77, 101].
