scholarly journals Circulating Levels of Free 25(OH)D Increase at the Onset of Rheumatoid Arthritis

2019 ◽  
Author(s):  
Vidyanand Anaparti ◽  
Xiaobo Meng ◽  
Hemsekhar Mahadevappa ◽  
Irene Smolik ◽  
Neeloffer Mookherjee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Linear Regression Analysis ◽  
Autoimmune Disorder ◽  
Joint Inflammation ◽  
Epidemiological Studies ◽  
Vitamin D Metabolites ◽  
Serum Samples ◽  
Hs Crp ◽  
Circulating Levels

ABSTRACTObjectiveEpidemiological studies suggest vitamin D deficiency as a potential risk factor for rheumatoid arthritis (RA) development, a chronic autoimmune disorder highly prevalent in indigenous North American (INA) population. We therefore profiled the circulating levels of 25-hydroxyvitaminD [25(OH)D], an active metabolite of vitamin D, in a cohort of at-risk first-degree relatives (FDR) of INA RA patients, a subset of whom subsequently developed RA (progressors).Methods2007 onward, serum samples from INA RA patients and FDR were collected at the time of a structured baseline visit and stored at −20°C. Anti-citrullinated protein antibodies (ACPA), 25(OH)D, hs-CRP, vitamin-D binding protein (VDBP) levels were determined using ELISA and rheumatoid factor (RF) seropositivity was determined by nephelometry.ResultsWe demonstrate that 25 (OH) D concentrations were lower in winter than summer (P=0.0538), and that serum 25(OH)D levels were higher in samples collected and stored after 2013 (P<0.0001). Analysis of samples obtained after 2013 demonstrated that 37.6% of study participants were 25(OH)D insufficient (<75nmol/L). Also, seropositive RA patients and FDR had lower 25(OH)D levels compared to ACPA-/FDR (P<0.05, P<0.01 respectively). Linear regression analysis showed 25(OH)D insufficiency was inversely associated with presence of RA autoantibodies. Longitudinal samples from 14 progressors demonstrated a consistent increase in 25(OH)D levels at the time they exhibited clinically detectable joint inflammation, without any significant change in VDBP levels.ConclusionWe demonstrate that 25(OH)D levels in serum increased at RA onset in progressors. The potential role that vitamin D metabolites and their downstream effects play in RA transition requires further investigation.

scholarly journals FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 904.1-904
Author(s):  
P. Vandormael ◽  
A. Pues ◽  
E. Sleurs ◽  
P. Verschueren ◽  
V. Somers
Keyword(s):  
Rheumatoid Arthritis ◽  
Therapy Response ◽  
Autoimmune Disorder ◽  
First Line ◽  
Research Support ◽  
Serum Samples ◽  
Glucocorticoid Treatment ◽  
Baseline Serum ◽  
Disease Remission ◽  
Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

scholarly journals Vitamin D Metabolites and Clinical Outcome in Hospitalized COVID-19 Patients

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2129
Author(s):  
Sieglinde Zelzer ◽  
Florian Prüller ◽  
Pero Curcic ◽  
Zdenka Sloup ◽  
Magdalena Holter ◽  
...  
Keyword(s):  
Vitamin D ◽  
Degradation Products ◽  
University Hospital ◽  
Vitamin D Metabolites ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Liquid Chromatography Tandem Mass ◽  
Relevant Role ◽  
Metabolite Ratio ◽  
The University

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 25,26(OH)2D3 were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19.

Serum concentration of vitamin D metabolites in rheumatoid arthritis

1987 ◽  
Vol 6 (2) ◽  
pp. 238-243 ◽  
Author(s):  
O. S. Als ◽  
B. Riis ◽  
C. Christiansen
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Serum Concentration ◽  
Vitamin D Metabolites

scholarly journals Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Muhammad M. Aslam ◽  
Peter John ◽  
Attya Bhatti ◽  
Sidrah Jahangir ◽  
M. I. Kamboh
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Immune Responses ◽  
Molecular Mechanisms ◽  
Genetic Factors ◽  
Autoimmune Disorder ◽  
Serum Levels ◽  
Principal Factor ◽  
Phosphate Homeostasis ◽  
Low Serum

Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.

scholarly journals The Relationship between Vitamin D Metabolites and Androgens in Women with Polycystic Ovary Syndrome

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1219
Author(s):  
Jakub Mesinovic ◽  
Helena J. Teede ◽  
Soulmaz Shorakae ◽  
Gavin W. Lambert ◽  
Elisabeth A. Lambert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Polycystic Ovary ◽  
Total Testosterone ◽  
Body Fat Percentage ◽  
Vitamin D Metabolites ◽  
Fat Percentage ◽  
Ovary Syndrome ◽  
Hs Crp ◽  
The Relationship

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m2). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D–androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population.

Circulating levels of calciotropic hormones during treatment with nasal salmon calcitonin

1991 ◽  
Vol 125 (2) ◽  
pp. 127-131 ◽  
Author(s):  
Gorm Thamsborg ◽  
Tommy L. Storm ◽  
Henrik Daugaard ◽  
Søren Schifter ◽  
Ole H. Sørensen
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Nasal Spray ◽  
Salmon Calcitonin ◽  
Serum Levels ◽  
Treated Group ◽  
Human Calcitonin ◽  
Vitamin D Metabolites ◽  
Calciotropic Hormones ◽  
Circulating Levels

Abstract. Circulating levels of calciotropic hormones were measured during one year of treatment with either 200 IU of salmon calcitonin daily or placebo as a nasal spray in 20 postmenopausal women with a former Colles' fracture. A supplement of 0.5 gram elemental calcium was given to all participants. Serum levels of parathyroid hormone and human calcitonin were determined with radioimmunoassays, and serum levels of vitamin D metabolites were determined with protein binding assays. We did not find any significant differences between the two groups with respect to serum levels of calciotropic hormones. In the salmon calcitonin treated group there was a tendency towards a small decrease in serum levels of human calcitonin and an increase in serum levels of calcitriol. Our results suggest that treatment with 200 IU of salmon calcitonin daily as a nasal spray does not markedly affect fasting serum levels of parathyroid hormone, human calcitonin, and vitamin D metabolitis.

Elevated 1,25-dihydroxyvitamin D3 and intestinal calbindin-D9k in the toothless rat

1990 ◽  
Vol 258 (2) ◽  
pp. E377-E381
Author(s):  
M. F. Seifert ◽  
R. W. Gray ◽  
M. E. Bruns
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Morphological Evidence ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Calbindin D9k ◽  
Plate Morphology ◽  
Circulating Levels ◽  
Phosphorus Levels

The toothless (tl) rat is a nonlethal osteopetrotic mutation characterized by systemic skeletal sclerosis, growth plate morphology suggestive of rickets, and morphological evidence of reduced osteoclastic bone resorption. Vitamin D metabolites, serum calcium and phosphorus levels, and the developmental appearance of vitamin D-dependent intestinal calcium binding protein (calbindin-D9k) was studied in normal and mutant rats of tl stock from 7 to 35 days of age. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was found to be significantly elevated in mutant animals by 7 days of age (71 +/- 9 pM, tl/tl vs. 24 +/- 8 pM, +/?) and continued to increase to a peak of 428 pM at the time of weaning. This was 240% higher than normals at this period. The elevated levels of 1,25-(OH)2D3 stimulated a significant and precocious appearance of intestinal calbindin-D9k in mutants, beginning by 14 days of age and reaching their peak levels at 21 days postpartum (25.6 +/- 1.7 micrograms/mg protein, tl/tl vs. 16.4 +/- 1.5 micrograms/mg protein, +/?). The cause of the elevated circulating levels of 1,25-(OH)2D3 in tl rats is unknown but may be due to the low serum phosphorus levels present in these animals.

scholarly journals MON-386 Determining Vitamin D Status: Analytical Variability Between Available Assays

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Azni Lihawa Abdul Wahab ◽  
Hans Gerhard Schneider
Keyword(s):  
Vitamin D ◽  
Cross Reactivity ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Serum Samples ◽  
Hydroxyvitamin D ◽  
Low Concentrations ◽  
Strong Positive Relationship ◽  
Liquid Chromatography Tandem Mass ◽  
25 Hydroxyvitamin D

Abstract Clinical interest to evaluate serum 25-hydroxyvitamin D[25(OH)D] to assess Vitamin D status in health risks continue to increase exponentially over the last decade. Variability of 25(OH)D measurements remains controversial despite the international initiative Vitamin D Standardization Program (VDSP) to standardise the assays. The aim of the present study was to examine the correlation of 25(OH)D concentrations measured by different assays. We measured 25(OH)D using the new Abbott Alinity and DiaSorin LiaisonXL chemiluminescence immunoassays against the National Institute of Standards and Technology (NIST)-traceable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The immunoassay method were compared with the LC-MS/MS using Passing-Bablok regression and Bland-Altman analysis. Common 25(OH)D cut-point for classification of vitamin D deficiency was used to compare the different assays. 125 adult serum samples were randomly selected and measured 25(OH)D levels ranged between &lt;10 nmol/L to 290 nmol/L as determined by LC-MS/MS. Compared to the LC-MS/MS, both immunoassays demonstrated strong positive relationship based on Passing-Bablok regression analysis. The results were as follows: Abbott Alinity = 0.85x + 1.29nmol/L, 95% CI: -2.39 to 5.03 (r=0.94); DiaSorin LiaisonXL= 0.74x + 2.54nmol/L, 95% CI: -2.53 to 6.18 (r=0.91). Despite apparent good correlation, the overall mean bias was -12.6% for Abbott Alinity and -24.4% for DiaSorin LiaisonXL assays. A higher percentage of patients were classified as vitamin D deficient (25(OH)D &lt;50 nmol/L) using DiaSorin LiaisonXL (53%) followed by Abbott Alinity (49%), when compared with LC-MS/MS (34%). Using 25(OH)D ≥ 50nmol/L as “adequate” determined by LC-MS/MS method, 22% (18/82) and 28% (23/82) of patients were classified as “deficient” when analysed on Abbott Alinity and DiaSorin LiaisonXL respectively. Clinician should be aware of the inter-method variability among different Vitamin D assays despite standardization efforts. These differences could be due to cross-reactivity with 25(OH)D2 and vitamin D metabolites, such as 24,25(OH)2D and epimeric forms. 3-epi-25(OH)D is not separated chromatographically by the LC-MS/MS method used in this study. Therefore, the negative bias observed might be due to interference from the 3-epi-25(OH)D, whereby clinical significance is uncertain. It is present in low concentrations in adult human serum, 1 but seen in significant amounts in neonatal serum.2 It is advisable to monitor serum 25(OH)D level following treatment in the same laboratory. 1. Lensmeyer G, et al. The C-3 epimer of 25-hydroxyvitamin D3 is present in adult serum. JCEM 2012; 97: 163–8. 2. Singh RJ, et al. C-3 epimers can account for a significant portion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. JCEM 2006; 91: 3055-61.

Simultaneous measurement of 13 circulating vitamin D3 and D2 mono and dihydroxy metabolites using liquid chromatography mass spectrometry

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Carl Jenkinson ◽  
Reena Desai ◽  
Andrzej T. Slominski ◽  
Robert C. Tuckey ◽  
Martin Hewison ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Vitamin D ◽  
Liquid Chromatography ◽  
Human Serum ◽  
High Sensitivity ◽  
Reference Level ◽  
Vitamin D Metabolites ◽  
Serum Samples ◽  
Human Serum Samples ◽  
Limit Of Quantitation

Abstract Objectives Clinical evaluation of vitamin D status is conventionally performed by measuring serum levels of a single vitamin D metabolite, 25-hydroxyvitamin D predominantly by immunoassay methodology. However, this neglects the complex metabolic pathways involved in vitamin D bioactivity, including two canonical forms D3 and D2, bioactive 1,25-dihydroxy metabolites and inactive 24-hydroxy and other metabolites. Methods Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can measure multiple analytes in a sample during a single run with high sensitivity and reference level specificity. We therefore aimed to develop and validate a LC-MS/MS method to measure simultaneously 13 circulating vitamin D metabolites and apply it to 103 human serum samples. Results The LC-MS/MS method using a Cookson-type derivatization reagent phenyl-1,2,4-triazoline-3,5-dione (PTAD) quantifies 13 vitamin D metabolites, including mono and dihydroxy-metabolites, as well as CYP11A1-derived D3 and D2 metabolites in a single run. The lower limit of quantitation was 12.5 pg/mL for 1,25(OH)2D3 with accuracy verified by analysis of National Institute of Standards and Technology (NIST) 972a standards. Quantification of seven metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, 20(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3 and 1,20S(OH)2D3) was consistently achieved in human serum samples. Conclusions This profiling method can provide new insight into circulating vitamin D metabolite pathways forming the basis for improved understanding of the role of vitamin D in health and disease.

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