Eppur Si Muove: vitamin D is essential in preventing and modulating SLE

Azrielant, Shir; Shoenfeld, Yehuda

doi:10.1177/0961203316629001

Cited by 30 publications

(16 citation statements)

References 88 publications

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“…13,[40][41][42] However, interventional studies did not reach definite conclusions regarding the clinical efficacy of vitamin D treatment to treat SLE. 43 Our results are in agreement with another study, which showed that the levels of 25(OH)D were negatively associated with IFN-γ levels. 44 It was demonstrated that 25(OH)D suppresses adaptive immunity, which leads to the inhibition of proliferation and differentiation of CD4 + Th0 cells into Th1 and Th17 cells.…”

Section: Discussionsupporting

confidence: 93%

“…Although SLE patients are commonly photosensitive and, therefore, may have a greater 25(OH)D deficiency than the general population, 39 in the present study most of the patients have been treated with vitamin D (data not shown), because clinically, it was found that vitamin D deficiency may affect disease activity 13 , 40 , 41 , 42 . However, interventional studies did not reach definite conclusions regarding the clinical efficacy of vitamin D treatment to treat SLE 43 . Our results are in agreement with another study, which showed that the levels of 25(OH)D were negatively associated with IFN‐γ levels 44 .…”

Section: Discussionmentioning

confidence: 53%

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Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

et al. 2017

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The aims of this study were to delineate cytokine profiles of systemic lupus erythematosus (SLE), construct prediction models for diagnosis and disease activity using those profiles, and to examine the associations between TNFB Ncol polymorphism, body mass index (BMI) and vitamin D levels with cytokine levels. Two hundred SLE patients and 196 healthy controls participated in this case-control study. Plasma cytokines levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL- 4, IL-6, IL-10, IL-12 and IL-17 were measured and cytokines profiles were computed. IL-6, IL-12, IL-17, IFN-γ and IL-10 levels were significantly higher in SLE, while IL-4 was lower in SLE. The Th1/Th2 and Th1+Th17/Th2 profiles were significantly higher in SLE than in healthy controls, whereas there were no significant differences in the proinflammatory cytokine profile (TNFα+IL-6+IL-1β). In total, 90.4% of all subjects were correctly classified using Th1+Th17 profile and IL-10 (positively associated) and IL-4 (negatively associated) as predictor variables (sensitivity=66.7% and specificity=96.9%). In all, 20.9% of the variance in the SLE Disease Activity Index was predicted by the Th1+Th17/Th2 ratio, IL-10 and BMI (all positively) and proinflammatory profile (inversely associated). B1/B1 genotype is accompanied by increased IL-17 and Th17/Th2 ratio, while B1/B2 genotype is accompanied by higher IL-4 and IFNγ values. 25-OH vitamin D was inversely associated with IFN-γ levels. SLE is accompanied by Th1, Th17 and Treg profile and lowered IL-4 production. Lowered vitamin D levels and B1/B1 genotype, but not BMI, contribute to changes in cytokines profiles. Future treatments should target Th1, Th2 and Th17 profiles rather than inflammatory cytokines.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 53%

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

et al. 2017

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“…1 2 In rheumatic diseases in particular, 1,25[OH] 2 D regulates both innate and adaptive immunity, potentiating the innate response, [53][54][55][56] which has been shown to precede the development of autoimmunity in SLE, 57 but reducing adaptive immunity, 53-56 including reduced T cell activation 58 and working in conjunction with glucocorticoids on the inhibition of lymphocyte proliferation. 56 Vitamin D deficiency seems to play a role in increasing B cell activation 14 59 and therefore autoantibody production, and long-term supplementation with vitamin D increased the number of T-regulator cells in individuals with SLE.…”

Section: [Oh]mentioning

confidence: 99%

Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus

et al. 2016

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Objective We examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE. Methods 436 individuals who reported having a relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (± 3.9) years later. Fifty-six individuals transitioned to SLE (≥4 cumulative ACR criteria). 25-hydroxyvitamin D (25[OH]D) levels were measured by ELISA. Six single nucleotide polymorphisms (SNPs) in four vitamin D genes were genotyped. Generalized estimating equations, adjusting for correlation within families, were used to test associations between the vitamin D variables and the outcome of transitioning to SLE. Results Mean baseline 25[OH]D levels (p=0.42) and vitamin D supplementation (p=0.65) were not different between those who did and did not transition to SLE. Vitamin D deficiency (25[OH]D <20 ng/ml) was greater in those who transitioned compared to those who did not transition to SLE (46% versus 33%, p=0.05). The association between 25[OH]D and SLE was modified by CYP24A1 rs4809959, where for each additional minor allele, increased 25[OH]D was associated with decreased SLE risk: 0 minor alleles (adjusted OR:1.03, CI:0.98,1.09), 1 minor allele (adjusted OR:1.01, CI:0.97,1.05), 2 minor alleles (adjusted OR:0.91, CI:0.84,0.98). Similarly, vitamin D deficiency significantly increased the risk of transitioning to SLE in those with two minor alleles at rs4809959 (adjusted OR:4.90, CI: 1.33,18.04). Conclusions Vitamin D status and CYP24A1 may have a combined role in the transition to SLE in individuals at increased genetic risk for SLE.

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“…Systemic lupus erythematosus (SLE) is one of the most challenging rheumatic disorders that is possibly influenced by VitD. Despite some contradictory findings, several studies have reported significantly lower serum VitD levels in SLE patients [43][44][45]. Recent data indicated that these lower levels were also associated with an increased risk for moderate to severe SLE manifestations in patients [46].…”

Section: Vitamin D Status In Inflammatory Rheumatic Disordersmentioning

confidence: 99%

Vitamin D Deficiency and Rheumatoid Arthritis

Ishikawa

Colavite

Fraga-Silva

et al. 2016

Clinic Rev Allerg Immunol

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Vitamin D (VitD) is a hormone primarily synthesized in human skin under the stimulation of ultraviolet radiation. Beyond its endocrine role in bone metabolism, VitD is endowed with remarkable immunomodulatory properties. The effects of VitD on the immune system include the enhancement of microbicidal ability of monocytes/macrophages and the down-modulation of inflammatory cytokines produced by T lymphocytes. VitD deficiency is involved in many health problems, including immune-mediated diseases such as autoimmune disorders. Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease that compromises the joints, causing cartilage destruction and bone erosion. RA treatment usually consists of combined therapies that generally suppress the entire immune response leading to increased susceptibility to infections. This review describes the main effects of VitD on innate and adaptive immune system and also VitD status in inflammatory rheumatic diseases such as RA. Despite some controversies, the majority of reports reinforce the idea that lower VitD levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. Therefore, supplementation with VitD to achieve normal serum levels is worthwhile as an aforethought. Original data concerning the potential applicability of 1,25-dihydroxyvitamin D (VitD3), the active form of vitamin D, as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3 associated with proteoglycan (PG), which is a specific cartilage antigen, was tested in the course of experimental arthritis. This association significantly lowered clinical scores and local histopathological alterations. Even though local analysis of T cell subsets and cytokine production did not reveal any difference between the experimental groups, VitD3+PG association significantly reduced cytokine production by spleen cells. These results suggest that VitD3 played a role as a tolerogenic adjuvant by down-modulating the course of experimental RA. Considering this tolerogenic effect of VitD3+PG association, further investigations will reveal its plausible use in human RA.

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Eppur Si Muove: vitamin D is essential in preventing and modulating SLE

Cited by 30 publications

References 88 publications

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

Cytokines in systemic lupus erythematosus: far beyond Th1/Th2 dualism lupus: cytokine profiles

Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus

Vitamin D Deficiency and Rheumatoid Arthritis

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