Free vitamin D₃ index and vitamin D‐binding protein in multiple sclerosis: A presymptomatic case–control study

Abstract

Background and purpose High levels of 25‐hydroxyvitamin D3 (25[OH]D3) are associated with a lower risk for multiple sclerosis (MS). The bioavailability of 25(OH)D3 is regulated by its main plasma carrier, vitamin D‐binding protein (DBP). Free 25(OH)D3 can be estimated by also measuring DBP concentration. In addition, DBP has immunomodulatory functions that may independently affect MS pathogenesis. No previous studies have assessed free 25(OH)D3 or DBP in presymptomatically collected samples. This study was undertaken to assess free 25(OH)D3 and DBP as risk factors for MS. Methods A nested case–control study was performed with presymptomatic serum samples identified through cross‐linkage of MS registries and Swedish biobanks. Concentration of 25(OH)D3 was measured with liquid chromatography and DBP levels with sandwich immunoassay. Free 25(OH)D3 was approximated as free vitamin D3 index: (25[OH]D3/DBP) × 103. MS risk was analyzed by conditional logistic regression, calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results Serum samples from 660 pairs of matched cases and controls were included. At <20 years of age, high levels of free vitamin D3 index were associated with a lower risk of MS (highest vs. lowest quintile: OR = 0.37, 95% CI = 0.15–0.91, p for trend across quintiles = 0.04). At age 30–39 years, high levels of DBP were associated with a lower MS risk (highest vs. lowest quintile: OR = 0.36, 95% CI = 0.15–0.85, p for trend = 0.02). Conclusions These findings support the hypothesis that high levels of free 25(OH)D3 at a young age reduce the risk of MS later in life. They also implicate a role for DBP in MS etiology.

Association of Blood Levels of Vitamin D and Its Binding Protein with Clinical Phenotypes of Multiple Sclerosis

“…In the current study, the plasma level of DBP was significantly lower in patients than in the healthy controls and lowest in the RRMS-relapse group. This is consistent with previous observations [12][13][14]. Some other studies reported no change in circulating DBP in relapsing MS during remission and relapse [16] and during remission [12] as compared to healthy controls, while at least one study [18] reported higher DBP levels in RRMS.…”

“…The association of changing levels of DBP with the presence of MS is, however, controversial. Various studies have suggested that DBP levels are (i) low in MS patients' cerebrospinal fluid (CSF), especially in those patients with relapsing MS [10,11]; (ii) low in the serum of patients with MS compared to the serum of healthy controls [12], and the lowest in relapsing-remitting (RRMS) patients [13,14]; (iii) higher in the CSF of patients with secondary progressive MS (SPMS) [15]; (iv) not different in the serum levels in patients with stable or active disease compared to the serum levels of controls [16,17]; and (v) according to at least one study [18], higher in RRMS patients. The implications of low DBP's association with low circulating free vitamin D are unclear.…”

Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes

“…There is evidence for an immunomodulatory role of vitamin D in multiple sclerosis [ 35 ]. Other studies have demonstrated some utility of vitamin D binding protein in distinguishing people with multiple sclerosis versus controls [ 36 , 37 ], or risk of developing multiple sclerosis [ 38 ]. Vitamin D binding protein has been shown to be expressed on spinal cord neurons, pia mater and grey matter within the brains of people with multiple sclerosis, and in an animal model of multiple sclerosis, high vitamin D binding protein appeared to mitigate beneficial effects of vitamin D3 supplementation and inhibit recovery [ 37 ].…”

The Role of Vitamin D in Multiple Sclerosis

“…Başka bir araştırmada ise 20 yaşından küçük bireylerde yüksek serbest D3 vitamin indeksi daha düşük MS riski ile ilişkilendirilirken 30-39 yaş aralığında yüksek VDBP seviyeleri daha düşük MS riski ile ilişkilendirilmiştir. Bu durum MS etiyolojisinde VDBP'nin rolünün de önem arz ettiğini ortaya koymaktadır (18). D vitamini aktif forma dönüştükten sonra biyolojik fonksiyonlarını yerine getirebilmesi için, T hücreleri, dendritik hücreler, monositler, makrofajlar, ve aktif B hücreleri dahil olmak üzere hemen hemen tüm bağışıklık hücrelerinin çekirdeğinde bulunan D vitamini reseptörüne (VDR) bağlanması gerekir (12).…”