Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers

Abstract

<b><i>Background:</i></b> Over the past decade, several controversial studies described a relationship between vitamin D and atopic diseases. Low plasma vitamin D levels or even vitamin D deficiency was associated with an increased incidence of atopic disease, postulating that a higher dietary intake of vitamin D may be a beneficial strategy against atopic diseases such as atopic dermatitis (AD). <b><i>Objective:</i></b> Our aim was to determine the relationship between plasma 25-hydroxyvitamin D3 (25(OH)D<sub>3</sub>) levels, the levels of the ligand of the vitamin D receptor (VDR) heterodimerization partner as well as the retinoid X receptor (RXR) and the active vitamin A5 derivative 9-<i>cis</i>-13,14-dihydroretinoic acid (9CDHRA) and AD severity. <b><i>Methods/Results:</i></b> Samples from AD patients (<i>n</i> = 20) and healthy volunteers (<i>n</i> = 20) were assessed. In our study, the frequently measured VDR ligand precursor 25(OH)D<sub>3</sub> in addition to the VDR-ligand 1,25-dihydroxyvitamin D3 (1,25(OH)<sub>2</sub>D<sub>3</sub>) and 9CDHRA displayed no different levels when compared with the plasma of AD patients and healthy volunteers. When performing further correlation studies focusing on AD patients, plasma 25(OH)D<sub>3</sub> levels showed a negative correlation with eosinophils in blood (EOS) and SCORing Atopic Dermatitis (SCORAD) values, while 1,25(OH)<sub>2</sub>D<sub>3</sub> and 9CDHRA levels correlated positively with plasma IgE, EOS, and SCORAD values. <b><i>Conclusion:</i></b> In consequence, the metabolic activation of vitamin D from 25(OH)D<sub>3</sub> towards 1,25(OH)<sub>2</sub>D<sub>3</sub> as well as the co-liganding of the RXR by 9CDHRA may be an important signalling mechanism, an important marker for AD development and severity as well as the basis for novel nutritional and pharmaceutical AD treatment options.

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles

“…In addition, metabolic signatures have identified therapeutic responders as shown for omalizumab and dupilumab treatments [ 132 , 133 ]. Only recently, the increased levels of vitamin D and A5 ligands in the plasma of AD patients has been postulated as a biomarker of AD severity [ 134 ].…”

Causal Associations between Vitamin D Levels and Psoriasis, Atopic Dermatitis, and Vitiligo: A Bidirectional Two-Sample Mendelian Randomization Analysis

“…These findings suggest that vitamin D might play a role in calcium homeostasis, immune regulation, anti-bacterial, and anti-inflammation. Early epidemiological studies have reported associations of blood 25(OH)D or 25(OH)D 3 levels with psoriasis, atopic dermatitis, and vitiligo [10][11][12], but concluded conflicting association results [13][14][15][16]. For example, Ng et al found a significantly lower blood 25(OH)D level in atopic dermatitis patients than healthy controls and low serum vitamin D levels were associated with disease severity [10].…”

“…Vitamin D supplementation might improve disease manifestation [17][18][19] and decrease the risk of psoriasis [20]. However, Lucas et al suggested no statistically significant difference of blood 25(OH)D 3 levels between atopic dermatitis patients and controls [13]. A cohort study of 4378 children indicated that low 25(OH)D levels at the age of two years old was not a risk factor for the development of atopic dermatitis at age of three years of age [14].…”