Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1600-1615 ◽  
Author(s):  
D J Go ◽  
J Y Lee ◽  
M J Kang ◽  
E Y Lee ◽  
E B Lee ◽  
...  

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

2020 ◽  
Vol 8 (2) ◽  
pp. 89-93
Author(s):  
Roya Moloudinia ◽  
Gelavij Mahmoodi ◽  
Mohammad Abdi ◽  
Sabrieh Amini ◽  
Shirin Ferdowsi

Background: Several studies have indicated that polymorphism in vitamin D pathway genes is associated with breast cancer (BC) risk. Vitamin D-binding protein (VDBP) is a vital element in the metabolism of the vitamin D. VDBP carries the serum 25(OH) D3 to cells to promote vitamin D biological functions, such as cell proliferation and apoptosis. Missense SNP (rs.7041) is a common polymorphism in VDBP gene, which shows ethnic-specific allele frequencies. Objectives: This study presents the correlation of the rs7041 (Asp432Glu) gene polymorphism and plasma concentrations of VDBP in Kurdish patients with BC in Sanandaj, Iran. Methods: This cross-sectional study included 44 premenopausal BC patients and 44 healthy subjects. Plasma VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). The VDBP (rs7041) was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: VDBP level was associated with a non-significant risk of BC (P=0.397). Frequencies of individuals with VDBP (rs7041) TT, TG, and GG genotypes were 13.6%, 52.2%, and 34.09% in case group and 11.3%, 79.5%, and 9.9% in control group, respectively. Genotype GG associated with increased susceptibility to developing BC (odds ratio [OR]=5.172, CI: 1.555-17.2, P=0.007). There was a significant reverse correlation between GT genotype and BC (OR=0.282, 95% CI: 0.110-0.722, P=0.008) Conclusion: The changes in the vitamin D pathway may increase susceptibility to develop BC in the Iranian Kurdish population.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Leila Setayesh ◽  
Krista Casazza ◽  
Nariman Moradi ◽  
Sanaz Mehranfar ◽  
Habib Yarizadeh ◽  
...  

Abstract Objective Equivocal association the contribution of 25-hydroxyvitamin D (25(OH)D) and the well-accepted role of vitamin D-binding protein (VDBP) on bioavailability of 25(OH)D or its independent roles, has led to possible association of the VDBP in glucose metabolism. This study was conducted to evaluate the relationships among 25(OH)D, VDBP, glucose/insulin metabolism and homeostatic model assessment (HOMA-IR). Blood samples were collected from 236 obese and overweight women. VDBP and 25(OH)D levels, and biochemical parameters were measured using an enzyme-linked immunosorbent assay (ELISA). An impedance fat analyzer was utilized to acquire the body composition. Results Using the multivariate linear regression, a reverse relationship was observed between VDBP and (HOMA-IR), such that women with higher VDBP displayed lower insulin resistance. The relationship was independent of age, body mass index, standardized energy intake and physical activity (p = 0.00). No significant relationship between 25(OH)D levels, FBS, body composition or insulin resistance were observed (p > 0.2). Current study observed that higher level of VDBP may be associated with lower levels of insulin and HOMA-IR, thus the evaluation of VDBP in diverse population groups seems to have significant clinical value in evaluating the prevalence of DM or early stage of glucose intolerance.


Author(s):  
DJ Go ◽  
JY Lee ◽  
MJ Kang ◽  
IA Choi ◽  
EY Lee ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sanglin Li ◽  
Lina Hu ◽  
Chanyu Zhang

Abstract Background Ovarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve. Methods Urine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis. Results When Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS. Conclusions Urinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2853 ◽  
Author(s):  
Mayeli M. Martínez-Aguilar ◽  
Diana I. Aparicio-Bautista ◽  
Eric G. Ramírez-Salazar ◽  
Juan P. Reyes-Grajeda ◽  
Aldo H. De la Cruz-Montoya ◽  
...  

Osteoporosis is a skeletal disease mainly affecting women over 50 years old and it represents a serious public health problem because of the high socioeconomic burden. This disease is characterized by deterioration of bone microarchitecture, low bone mineral density (BMD), and increased risk of fragility fractures. This study aimed to identify serum useful proteins as biomarkers for the diagnosis and/or prognosis of osteoporosis and fracture risk. We collected 446 serum samples from postmenopausal women aged ≥45 years old. Based on the BMD measurement, we classified the participants into three groups: osteoporotic, osteopenic, and normal. In an initial discovery stage, we conducted a proteomic approach using two-dimensional differential gel electrophoresis (2D-DIGE). The peptides into the spots of interest were identified through matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF/TOF). Enzyme-linked immunosorbent assay (ELISA) was performed to validate the proteins of interest. We identified 27 spots of interest when comparing low BMD versus normal BMD postmenopausal women. Based on their relevance in bone metabolism, we analyzed three proteins: ceruloplasmin (CP), gelsolin (GSN), and vitamin D-binding protein (VDBP). Our results demonstrated that low serum VDBP levels correlate with low BMD (osteopenic and osteoporotic). Therefore, VDBP could be considered as a novel, potential, and non-invasive biomarker for the early detection of osteoporosis.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2495
Author(s):  
Melinda Fernando ◽  
Thisara G. Coster ◽  
Stacey J. Ellery ◽  
Deborah de Guingand ◽  
Siew Lim ◽  
...  

Maternal vitamin D deficiency has been associated with adverse neonatal outcomes, however, existing results are inconsistent. Current data focus on total 25-hydroxyvitamin D (25(OH)D) as the common measure of vitamin D status, while additional measures including vitamin D-binding protein (VDBP) and free and bioavailable metabolites have not been explored in relation to neonatal outcomes. We examined whether VDBP and total, free, and bioavailable vitamin D metabolites in early pregnancy are associated with subsequent neonatal outcomes. In this retrospective analysis of 304 women in early pregnancy (<20 weeks gestation), demographic and anthropometric data were collected and total 25(OH)D (chemiluminescent assay), VDBP (polyclonal enzyme-linked immunosorbent assay (ELISA)) and albumin (automated colorimetry) were measured in bio-banked samples. Free and bioavailable 25(OH)D were calculated using validated formulae. Neonatal outcomes were derived from a medical record database. Higher maternal total and free 25(OH)D concentrations were associated with higher neonatal birthweight (β = 5.05, p = 0.002 and β = 18.06, p = 0.02, respectively), including after adjustment for maternal covariates including age, body mass index (BMI) and ethnicity (all p ≤ 0.04). Higher total 25(OH)D and VDBP concentrations were associated with a lower likelihood of neonatal jaundice (odds ratio [OR] [95%CI] = 0.997 [0.994, 1.000], p = 0.04 and 0.98 [0.96, 0.99], p = 0.03, respectively), but these were attenuated after adjustment for the above maternal covariates (both p = 0.09). Our findings suggest a novel association between free 25(OH)D and neonatal birthweight. Total 25(OH)D concentrations were also associated with birthweight, and both total 25(OH)D and VDBP were associated with jaundice, but the latter were not significant after adjustment. These results suggest a potential link between these metabolites and neonatal outcomes; however, further large-scale prospective studies are warranted.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Xin Zhang ◽  
Huanxin Meng ◽  
Li Xu ◽  
Li Zhang ◽  
Dong Shi ◽  
...  

Vitamin D-binding protein (DBP) is the main transport protein of vitamin D and plays an important role in the immune system and host defenses. The purpose of this study was to measure DBP levels in plasma and gingival crevicular fluid (GCF) of patients with generalized aggressive periodontitis (GAgP), in comparison to healthy controls, with the goal of elucidating the relationship between DBP and GAgP. Fifty-nine GAgP patients and 58 healthy controls were recruited for the study; clinical parameters of probing depths (PD), bleeding index, and attachment loss (AL) were recorded. DBP levels were measured by enzyme-linked immunosorbent assay. From the results, GAgP patients had higher plasma DBP concentrations (P<0.001) but lower GCF DBP concentrations (P<0.001) than healthy controls. In GAgP group, after controlling the potential confounders of age, gender, smoking status, and BMI index, GCF DBP concentrations correlated negatively with PD (P<0.001) and AL (P=0.009). Within the limits of the study, we concluded that decreased GCF DBP level and increased plasma DBP level are associated with periodontitis.


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