Meta AnalysisID 1565
维生素D、维生素A、烟酸和短链脂肪酸及其衍生物在增加炎症或自身免疫性疾病患者循环调节性T细胞数量和调节调节性T细胞表型中的作用
CRD42016048648
We have shown that recipients of a haematopoietic stem cell graft with a higher proportion of T regulatory cells to total CD3+ or CD4+ T cells have a very substantially improved clinical outcome (Danby et al, Bone Marrow
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- Meta Analysis Id
- 1565
- Evidence Id
- 10123
- Core Evidence Id
- 10123
- Source Meta Analysis Id
- 1519
- Herb2 Meta Analysis Id
- HBMA001519
- Crd Id
- CRD42016048648
- Title
- The role of vitamin D, vitamin A, niacin and short-chain fatty acids and their derivatives in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory or autoimmune disease
- Review Question
- We have shown that recipients of a haematopoietic stem cell graft with a higher proportion of T regulatory cells to total CD3+ or CD4+ T cells have a very substantially improved clinical outcome (Danby et al, Bone Marrow Transplantation 2015, 21 Sept). Our data suggest a 40% difference in survival between recipients with the highest and lowest quartiles of Treg/CD4 ratios. There is a substantial body of animal work and observational work in humans that higher vitamin D levels are associated with higher Treg/total T cell ratios and a more immunosuppressive phenotype (Adams et al. Clin Endocrinol Metab. 2010, 95(2):471-8; Hewison et al. Rev Endocr Metab Disord. 2001, 2(2):217-27; Khoo et al. PLoS One. 2012; 7(1):e29250; Prietl et al. Isr Med Assoc J. 2010, 12(3):136-9).Several small studies have shown that short courses of high dose vitamin D as oral Vitamin 25 (OH) D3 can increase the Treg/CD4 or Treg CD3 ratio, absolute Treg concentrations in peripheral blood and the functional capacity of Tregs to supress effector cells in healthy individuals (Bock et al. Diabetes Metab Res Rev. 2011, 27(8):942-5; Prietl et al. Eur J Nutr. 2014, 53(3):751-9) and in patients with inflammatory or autoimmune diseases (Gabbay et al. Arch Pediatr Adolesc Med. 166(7):601-7; Piantoni et al. Lupus. 2015, 24(4-5):490-8; Treiber et al. Clin Immunol. 2015, 161(2):217-24). The function of Treg cells may also be increased by vitamin A supplements (Saboor-Yaraghi et al. J Mol Neurosci. 2015, 56(3):608-12). Moreover, the short chain fatty acid, butyrate, may be produced by the commensal gut flora and prime Treg cells in the secondary lymphoid tissue in the gastrointestinal tract (Arpaia et al. Nature 2013, 504(7480):451-5). In mice, exogenous butyrate or the vitamin niacin or similar compounds such as mono- or dimethyl-fumararte acting via GPR109a on lymphocytes, may increase Tregs levels and function (Bald et al, Nat Drug Discov Revs 2012, 40:603-619; Singh et al, Immunity 2014, 40:128-139). Finally, gamma-amino butyric acid (GABA) has been used experimentally to increase Tregs in animals but the effects of this butyrate derivative of Treg numbers and functions in humans is limited (Tian et al. PLoS ONE 6(9):e25338). There is an urgent need within the transplant community for simple efficacious methods to improve outcomes. Conditioning donors to improve the graft composition promises to be a simple, efficacious method to achieve substantially better outcomes. We wish to undertake a systematic review of randomised controlled trials to assess the efficacy of vitamin D, vitamin A, niacin and short-chain fatty acids and their derivatives in enhancing absolute Treg concentrations, Treg/Total T cell ratios, altered Treg phenotypes such as the ratio of naïve CD45RA+ Tregs to memory CD45RO+ Tregs, or Tregs expressing cutaneous or gut homing receptors (CLA1+ or alpha4beta7 integrin respectively) in patients with inflammatory or autoimmune disease.
- Study Type Included
- Randomised controlled trials which measure the absolute concentration or proportion of regulatory T cells. Studies which do not measure regulatory T cells will be excluded.
- Condition Being Studied
- The effect of vitamins on regulatory T cells in patients with inflammatory or autoimmune disease.
- Participant
- Patients with inflammatory or autoimmune disease.
- Animal
- Human Disease Modelled
- Intervention
- Vitamin D or vitamin A or niacin or nicotinic acid or mono- or dimethyl-fumararte or Acipimox; butyrate or butyric acid or gamma amino butyric acid or gamma amino butyrate or 3 hydroxy butyrate or 3 hydroxy butyric acid administered orally. If co-interventions are administered, we will include these only if administered to both/all trial arms.
- Comparator Control
- No intervention (control) or placebo.
- Main Outcome
- (i) Absolute concentration of regulatory T-cells measured in peripheral blood (ii) Proportion of regulatory T cells (as a proportion of CD4+ or CD3+ Tcells) measured in peripheral blood Measures of effect For each outcome we will record the mean and standard deviation in the treatment and control groups. For continuous outcomes using the same scale, we will assess mean difference (MD) with 95% CI intervals (CI). For continuous outcomes measured with different scales, we will present the standard mean difference (SMD). Study data will be grouped according to follow-up time points as determined by the available data. Where possible, outcomes will be analysed using mean change from baseline values. If insufficient mean change from baseline data are reported, we will analyse outcomes using endpoint data.
- Outcome Measure
- Additional Outcome
- (i) Treg suppressive capacity (e.g. inhibition of expansion of effector T cells) (ii) Correlation between serum vitamin D or vitamin A or niacin or short-chain fatty acid levels and the number or proportion of Tregs (iv) Safety measures (e.g. serum vitamin, serum calcium, C-reactive protein levels, excess infection or bleeding events) (v) Compliance Measures of effect For continuous outcomes we will record the mean and standard deviation, and for dichotomous outcomes we will record the number of events in the treatment and control groups. For continuous outcomes using the same scale, we will present the mean difference (MD) with 95% CI intervals (CI). For continuous outcomes measured with different scales, we will present the standard mean difference (SMD). For dichotomous outcomes, relative risks (RR) will be reported with a 95% CI. Study data will be grouped according to follow-up time points as determined by the available data. Where possible, continuous outcomes will be analysed using mean change from baseline values. If insufficient mean changes from baseline data are reported, we will analyse outcomes using endpoint data.
- Study Method
- Systematic review
- Keyword
- Autoimmune Diseases; Cell Count; Cholestanes; Fatty Acids; Humans; Niacin; Phenotype; Vitamin A; Vitamin D; Vitamins
- Contact
- Organisational Affiliation
- Funding Source
- Other Selection Criteria
- Final Publication
- Same Topic Review
- Published Protocol
- Review Type
- Language
- English
- Country
- Review Stage
- First Submission Date
- Registration Date
- Anticipated Start Date
- Anticipated Completion Date
- Title Cn
- 维生素D、维生素A、烟酸和短链脂肪酸及其衍生物在增加炎症或自身免疫性疾病患者循环调节性T细胞数量和调节调节性T细胞表型中的作用
- Title En
- The role of vitamin D, vitamin A, niacin and short-chain fatty acids and their derivatives in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory or autoimmune disease
- Bilingual Status
- complete