title: 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.
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.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Frankfurt am Main, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Rose
authors.forename: M
authors.initials: M
authors.lastname: Penna-Martinez
authors.forename: E
authors.initials: E
authors.lastname: Klahold
authors.forename: D
authors.initials: D
authors.lastname: Kärger
authors.forename: F
authors.initials: F
authors.lastname: Shoghi
authors.forename: H
authors.initials: H
authors.lastname: Kahles
authors.forename: M
authors.initials: M
authors.lastname: Bayer
authors.forename: E
authors.initials: E
authors.lastname: Hintermann
authors.forename: J M
authors.initials: JM
authors.lastname: Pfeilschifter
authors.forename: K
authors.initials: K
authors.lastname: Badenhoop
authors.forename: E
authors.initials: E
authors.lastname: Ramos-Lopez
authors.forename: U
authors.initials: U
authors.lastname: Christen
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008875:Middle Aged; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics; D014807:Vitamin D / Q000097:blood*
chemical_list: C063898:DBP protein, human; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D014807:Vitamin D; D015847:Interleukin-4; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase