Influence of the vitamin D plasma level and vitamin D-related genetic polymorphisms on the immune status of patients with type 1 diabetes: A pilot study

Pharmazentrum Frankfurt/ZAFES.
Clinical & Experimental Immunology (Impact Factor: 3.04). 02/2013; 171(2):171-85. DOI: 10.1111/cei.12013
Source: PubMed

ABSTRACT Vitamin D (VD) has been implicated in type 1 diabetes (T1D) by genetic and epidemiological studies. Individuals living in regions with low sunlight exposure have an increased T1D risk and VD supplementation reduced the risk in human individuals and mouse models. One possibility of how VD influences the pathogenesis of T1D is its immunomodulatory effect on dendritic cells (DC), which then preferentially activate regulatory T cells (T(regs) ). In the present pilot study, we collected blood samples from a small cohort of patients with T1D at baseline and months 6 and 12. VD-deficient patients were advised to supplement with 1000 IU/day VD. We found a considerable variation in the VD plasma level at baseline and follow-up. However, with higher VD plasma levels, a lower frequency of interleukin (IL)-4-producing CD8 T cells was observed. We further performed a comprehensive genotyping of 13 VD-related polymorphisms and found an association between VD plasma level and the genotype of the VD binding protein (DBP). The frequency of DC and T cell subsets was variable in patients of all subgroups and in individual patients over time. Nevertheless, we found some significant associations, including the 1,25-dihydroxyvitamin D(3) hydroxylase (CYP27B1) genotype with the frequency of DC subtypes. In summary, our preliminary results indicate only a limited influence of the VD plasma level on the immune balance in patients with T1D. Nevertheless, our pilot study provides a basis for a follow-up study with a larger cohort of patients.

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    • "Genotyping of IL28B was performed as described before [25]. For the determination of CYP2R1- (rs10741657), CYP27B1-(rs10877012) and DBP (rs4588 and rs7041) polymorphisms DNA was amplified with the respective primers, with PCR conditions and enzymes as previously described [26], [27]. The polymorphisms within the DHCR7 reductase-gene (rs12785878/C_32063037_10 and rs7944926/C_12043682_10), DBP (rs2282679/C_26407519_10) and CYP24A1- (rs6013897/C_22958084_10) were analyzed in the laboratory of molecular endocrinology of our department using Taqman assays in an ABI 7300 PCR System under the conditions recommended by the manufacturer (Applied Biosystems, Darmstadt, Germany) as previously described [26]. "
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    ABSTRACT: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.
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    Hormone and Metabolic Research 11/2013; 46(1). DOI:10.1055/s-0033-1358453 · 2.12 Impact Factor
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    ABSTRACT: Type 1 diabetes (T1D) is a T cell mediated autoimmune disease characterized by immune mediated destruction of the insulin-producing β cells in the islets of Langerhans. Dendritic cells (DC) have been implicated in the pathogenesis of T1D and are also used as immunotherapeutic agents. Plasmacytoid (p)DC have been shown to have both protective and pathogenic effects and a newly described merocytic DC population has been shown to break tolerance in the mouse model of T1D, the non-obese diabetic (NOD) mouse. We have used DC populations to prevent the onset of T1D in NOD mice and clinical trials of DC therapy in T1D diabetes have been initiated. In this review we will critically examine the recent published literature on the role of DC subsets in the induction and regulation of the autoimmune response in T1D.
    Frontiers in Immunology 12/2013; 4:415. DOI:10.3389/fimmu.2013.00415
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