25-Hydroxyvitamin D and Peripheral Immune Mediators: Results from Two Nationwide Danish Pediatric Cohorts

Steffen U Thorsen, Christian B Pipper, Kristin Skogstrand, Flemming Pociot, Jannet Svensson, Steffen U Thorsen, Christian B Pipper, Kristin Skogstrand, Flemming Pociot, Jannet Svensson

Abstract

(1) Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470 patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981-1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997-2005. A variety of peripheral immune mediators were measured and compared to total 25(OH)D levels (25(OH)D₂ + 25(OH)D₃). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH)D (10 nmol/L increase) and leptin (RC (95% confidence interval (CI)), 0.98 (0.96; 1.00)), and a positive association between 25(OH)D (10 nmol/L increase) and the chemokine, chemokine (c-x-c motif) ligand (CXCL) 8 (RC (95% CI), 1.07 (1.01; 1.13)); (4) Conclusion: CXCL8 and leptin have significant associations with levels of 25(OH)D in the newly diagnosed cohort. These results do not indicate a strong influence of 25(OH)D on the peripheral immunological or inflammatory signature.

Keywords: Adolescent; C-reactive protein; Child; Cytokines/immunology; Diabetes Mellitus, Type 1; Infant, Newborn; TREM1, human; mannose-binding lectin; vitamin D.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relative change in mean levels of immune mediators with 95% confidence bands by 10 nmol/L increase in 25(OH)D levels in the birth cohort—results from the full adjusted model. IL, interleukin; IFNγ, interferon gamma; TNFα, tumor necrosis factor alpha; TGFβ, transforming growth factor beta; CRP, c-reactive protein; MBL, mannose-binding lectin; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; CXCL, chemokine (c-x-c motif) ligand.
Figure 2
Figure 2
Relative change in mean levels of immune mediators with 95% confidence bands by 10 nmol/L increase in 25(OH)D levels in the newly diagnosed cohort—results from the full adjusted model. IL, interleukin; IFNγ, interferon gamma; TNFα, tumor necrosis factor alpha; TGFβ, transforming growth factor beta; CRP, c-reactive protein; MBL, mannose-binding lectin; sTREM-1, soluble triggering receptor expressed on myeloid cells-1; CXCL, chemokine (c-x-c motif) ligand; CCL, chemokine (c-c motif) ligand; CI, confidence interval.

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