Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency

Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001 ). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02 ), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; p < 0.04 ) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; p = 0.02 ) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02 ) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels ( r = − 0.26 ; p = 0.001 ) and urine proteins (mg/dL) ( r = − 0.39 ; p < 0.01 ). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count ( r = 0.30 ; p < 0.001 ) and negatively correlated with the glomerular filtration rate ( r = − 0.28 ; p = 0.001 ). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins ( r = 0.38 ; p < 0.01 ). The calcidiol deficiency ( OR = 2.27 ; 95% CI = 1.15 -4.49; p < 0.01 ), high calcitriol levels ( T 3 rd , OR = 4.19 , 95% CI = 2.23 -7.90; p < 0.001 ), and a high calcitriol/calcidiol ratio score ( T 3 rd , OR = 5.93 , 95% CI: 3.08-11.5; p < 0.001 ) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.

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Vitamin D in Colombian patients with systemic lupus erythematosus and its correlation with disease activity

Lupus ◽

10.1177/0961203320937783 ◽

2020 ◽

Vol 29 (10) ◽

pp. 1297-1304 ◽

Cited By ~ 1

Author(s):

Andrés F Cardona-Cardona ◽

Jairo A Cerón y Cerón

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Disease Activity ◽

Lupus Erythematosus ◽

Late Onset ◽

Activity Index ◽

Inverse Correlation ◽

Systemic Lupus ◽

Cross Sectional ◽

Low Levels

Introduction Patients with systemic lupus erythematosus (SLE) frequently present low levels of vitamin D. However, studies that have evaluated its association with disease activity have generated contradictory results. Methods A cross-sectional study was carried out on patients diagnosed with SLE in two hospitals in Manizales, Colombia. Disease activity was evaluated by the SLE disease activity index 2000 (SLEDAI-2K) and serum concentration of 25-hydroxyvitamin D (25(OH)D) was measured by chemiluminescence. The correlation analysis was accomplished with the Spearman correlation coefficient. Results The study included 51 patients. The median SLEDAI-2K score was 8 points. The mean serum level of 25(OH)D was 24.5 ng/ml. Of the participants, 37.3% had vitamin D insufficiency and 35.3% had deficiency. An inverse correlation was found between the levels of the 25(OH)D and the SLEDAI-2K score ( r = –0.578, p < 0.001), being greater in late-onset lupus, with absence of polyautoimmunity and in patients using glucocorticoids. Conclusions Low levels of vitamin D are frequent in SLE, presenting an inverse correlation with the disease activity. This is influenced by the use of glucocorticoids, the presence of late-onset lupus and the absence of polyautoimmunity.

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The Effect of Vitamin D Supplementation on Inflammatory and Hemostatic Markers and Disease Activity in Patients with Systemic Lupus Erythematosus: A Randomized Placebo-controlled Trial

The Journal of Rheumatology ◽

10.3899/jrheum.111594 ◽

2012 ◽

Vol 40 (3) ◽

pp. 265-272 ◽

Cited By ~ 107

Author(s):

ANNA ABOU-RAYA ◽

SUZAN ABOU-RAYA ◽

MADIHAH HELMII

Keyword(s):

Systemic Lupus Erythematosus ◽

Vitamin D ◽

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Vitamin D Supplementation ◽

Systemic Lupus ◽

Vitamin D Levels ◽

Before And After ◽

Hemostatic Markers

Objective.Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory autoimmune disease. Vitamin D has potent immunomodulatory properties that support its use in the treatment of autoimmune conditions, including SLE. We assessed vitamin D status in patients with SLE and determined alterations in inflammatory and hemostatic markers and disease activity before and after vitamin D supplementation.Methods.Patients with SLE (n = 267) were randomized 2:1 to receive either oral cholecalciferol 2000 IU/day or placebo for 12 months. Outcome measures included assessment of alterations in levels of proinflammatory cytokines and hemostatic markers, and improvement in disease activity before and after 12 months of supplementation. Disease activity was measured by the SLE Disease Activity Index. Vitamin D levels were measured by Liaison immunoassay (normal 30–100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels < 10 ng/ml as vitamin D deficiency.Results.The mean 25(OH)D level at baseline was 19.8 ng/ml in patients compared to 28.7 ng/ml in controls. The overall prevalence of suboptimal and deficient 25(OH)D serum levels among patients with SLE at baseline was 69% and 39%, respectively. Lower 25(OH)D levels correlated significantly with higher SLE disease activity. At 12 months of therapy, there was a significant improvement in levels of inflammatory and hemostatic markers as well as disease activity in the treatment group compared to the placebo group.Conclusion.Vitamin D supplementation in patients with SLE is recommended because increased vitamin D levels seem to ameliorate inflammatory and hemostatic markers and show a tendency toward subsequent clinical improvement. Clinical Trial Registry NCT01425775.

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The Association of Disease Activity, BMI and Phase Angle with Vitamin D Deficiency in Patients with IBD

Nutrients ◽

10.3390/nu11112583 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2583 ◽

Cited By ~ 2

Author(s):

Maria Chiara Mentella ◽

Franco Scaldaferri ◽

Marco Pizzoferrato ◽

Antonio Gasbarrini ◽

Giacinto Abele Donato Miggiano

Keyword(s):

Vitamin D ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Phase Angle ◽

Alimentary Tract ◽

Hypovitaminosis D ◽

Serum Levels ◽

Cross Sectional Study ◽

Cross Sectional ◽

Inflammatory Bowel

Hypovitaminosis D is frequently present in inflammatory bowel disease (IBD) with a higher incidence in Crohn’s disease (CD) than in Ulcerative Colitis (UC). Given the involvement of the alimentary tract, many factors can contribute to hypovitaminosis D. The aim of the study was to investigate the association of disease activity, body mass index (BMI) and phase angle with vitamin D deficiency in patients with IBD. A cross-sectional study was conducted on a cohort of 206 IBD patients (October 2016–September 2018). Of these patients, 32.6% were affected by hypovitaminosis D (CD: 38.6%; UC: 25.6%; p < 0.01). Negative and significant associations (p < 0.01) were found between BMI and vitamin D serum levels both in CD and UC patients. BMI represented a determinant of hypovitaminosis D (Odds Ratio (OR) = 1.12, p < 0.01) only in UC patients; phase angle was associated to hypovitaminosis D in both groups (CD: OR = 0.64, p < 0.05; UC: OR = 0.49, p < 0.01). Results of the present study confirm a higher incidence of hypovitaminosis D in patients with CD than in those with UC, and show that nutritional status plays a crucial role in the incidence of vitamin D deficiency in patients with IBD.

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Proprotein convertase subtilisin/kexin type 9 is related to disease activity and damage in patients with systemic erythematosus lupus

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20975904 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2097590

Author(s):

Hiurma Sánchez-Pérez ◽

Juan C. Quevedo-Abeledo ◽

Beatriz Tejera-Segura ◽

Laura de Armas-Rillo ◽

Iñigo Rúa-Figueroa ◽

...

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Cholesterol Metabolism ◽

Multivariable Analysis ◽

Density Lipoprotein ◽

Serum Levels ◽

Lipid Profiles ◽

Proprotein Convertase ◽

Cross Sectional ◽

Beta Coefficient

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that regulates cholesterol metabolism through low-density lipoprotein receptor degradation and that has been linked to cardiovascular (CV) disease. The purpose of the present study was to examine whether PCSK9 levels are disrupted compared with controls in patients with systemic lupus erythematosus (SLE). We additionally sought to establish whether PCSK9 is related to both the abnormalities in the lipid profile and to the disease activity or damage of patients with SLE. Methods: We performed a cross-sectional study that encompassed 366 individuals: 195 SLE patients and 171 age-, sex-, and statin intake-matched controls. PCSK9, lipoproteins serum concentrations, and lipid profiles were assessed in patients and controls. A multivariable analysis, adjusted for standard CV risk factors, was performed to evaluate the role of PCSK9 in SLE-related dyslipidemia. Results: Most lipid related-molecules were decreased in patients with SLE compared with controls. This downregulation included PCSK9, with PCSK9 levels being lower in patients than controls in the full multivariable analysis, including the modifications in lipid profiles that the disease itself produces {beta coefficient –73 [95% confidence interval (CI) –91 to –54] ng/ml, p ⩽ 0.001}. Both SLICC and SLEDAI scores were independently and positively related to PCSK9. Patients currently on hydroxychloroquine exhibited decreased levels of PCSK9 compared with those that were not taking hydroxychloroquine [beta coefficient –30 (95% CI −54 to −6) ng/ml, p = 0.015]. Conclusion: PCSK9 is downregulated in SLE compared with controls, but SLE patients with higher disease activity and damage exhibited higher PSCK9 serum levels.

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Systemic lupus erythematosus activity and beta two microglobulin levels

Sao Paulo Medical Journal ◽

10.1590/1516-3180.2014.1324703 ◽

2014 ◽

Vol 132 (4) ◽

pp. 239-242 ◽

Cited By ~ 5

Author(s):

Thelma Larocca Skare ◽

Kellen Ferri ◽

Marcela Aimone Santos

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Damage Index ◽

Serum Levels ◽

Course Evaluation ◽

Clinical Activity ◽

Systemic Lupus ◽

Correct Treatment

CONTEXT AND OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with a cyclical clinical course. Evaluation of the clinical activity of this disease is important for choosing the correct treatment. The objective of this study was to analyze the value of beta-2 microglobulin (β2M) serum levels in determining SLE clinical activity.DESIGN AND SETTING: Cross-sectional analytical study conducted at the rheumatology outpatient clinic of a private university hospital.METHODS: 129 SLE patients were studied regarding disease activity using SLEDAI (SLE Disease Activity Index) and cumulative damage using SLICC ACR (SLE International Collaborating Clinics/American College of Rheumatology Damage Index for SLE). At the same time, the β2M serum level, ESR (erythrocyte sedimentation rate), anti-dsDNA (anti-double-stranded DNA) and C3 and C4 complement fractions were determined.RESULTS: β2M levels correlated positively with SLEDAI (P = 0.02) and ESR (P = 0.0009) and negatively with C3 (P = 0.007). Patients who were positive for anti-dsDNA had higher β2M serum levels (P = 0.009).CONCLUSION: β2M levels are elevated in SLE patients with active disease.

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Serum Levels of T Cell Immunoglobulin and Mucin-Domain Containing Molecule 3 in Patients with Systemic Lupus Erythematosus

Journal of Clinical Medicine ◽

10.3390/jcm9113563 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3563

Author(s):

Tomoyuki Asano ◽

Naoki Matsuoka ◽

Yuya Fujita ◽

Haruki Matsumoto ◽

Jumpei Temmoku ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cell ◽

Renal Disease ◽

Disease Activity ◽

Lupus Erythematosus ◽

Serum Levels ◽

Organ Damage ◽

Enzyme Linked Immunosorbent Assay ◽

Clinical Parameters ◽

Systemic Lupus

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.

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Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17

Lupus ◽

10.1177/0961203316682095 ◽

2016 ◽

Vol 26 (9) ◽

pp. 917-926 ◽

Cited By ~ 12

Author(s):

D Shahin ◽

R M El-Farahaty ◽

M E Houssen ◽

S A Machaly ◽

M Sallam ◽

...

Keyword(s):

Vitamin D ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Signs ◽

Hypovitaminosis D ◽

Serum Levels ◽

High Serum ◽

Laboratory Markers ◽

Treatment Naïve ◽

25 Oh Vitamin D

Objectives The aim of this study was to assess the vitamin D status in treatment-naïve SLE patients and its association with clinical and laboratory markers of disease activity, including serum levels of IL-17 and IL-23. Methods Fifty-seven treatment-naïve SLE patients along with 42 matched controls were included. SLEDAI score was used to estimate disease activity. Serum levels of 25(OH) D, IL-17 and IL-23 were measured. Results The median level of 25(OH) D in SLE patients (40.8; 4–70 ng/ml) was significantly lower than in the controls (47; 25–93 ng/ml) ( P = 0.001). A total of 38.6% of SLE cases had 25 (OH) D levels < 30 ng/ml (hypovitaminosis D) vs. 4.8% of the controls ( P < 0.0001). Apart from thrombocytopenia, vitamin D was not associated with clinical signs of SLE. There were negative correlations between serum 25(OH) D and serum levels of IL-17, IL-23 and ANA (rho = −0.5, −0.8, −0.5, P ≤ 0.05) in SLE patients. Conclusion Hypovitaminosis D is prevalent in treatment naïve SLE patients. It contributes to ANA antibody production and is associated with high serum levels of IL-23 and IL-17; thus they may trigger the inflammatory process in SLE.

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The Usefulness of Endothelial Cell Adhesion Molecules and Anti-C1q Antibody in Monitoring Systemic Lupus Erythematosus Disease Activity

International Scholarly Research Notices ◽

10.1155/2014/275194 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6

Author(s):

Hasni Mahayidin ◽

Nurul Khaiza Yahya ◽

Wan Syamimee Wan Ghazali ◽

Asmahan Mohd Ismail ◽

Wan Zuraida Wan Ab Hamid

Keyword(s):

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Inverse Correlation ◽

Disease Activity Index ◽

Serum Levels ◽

Cross Sectional Study ◽

Cross Sectional ◽

Positive Correlations ◽

Global Disease Activity

Objectives. The study was conducted to determine the correlation of ICAM-1, VCAM-1, and anti-C1q antibody levels with SLE disease activity index (SLEDAI) and standard SLE disease activity immunological markers (anti-dsDNA and sera C3 and C4). Study Design. This was a cross-sectional study. Materials and Methods. Blood samples were obtained from 95 SLE patients (45 active SLE and 50 nonactive SLE) and 50 controls. The subjects were assessed using SLEDAI and score of more than five is determined as having active SLE. The sera were tested for serum ICAM-1, VCAM-1, and anti-C1q (ELISA), anti-dsDNA (CLIFT), serum C3, and serum C4 (immunonephelometry). Results. Anti-dsDNA and anti-C1q antibody showed good positive correlations with SLEDAI (r=0.529, P<0.001 and r=0.559, P<0.001, resp.). VCAM-1 and sera C3 and C4 showed fair correlation with SLEDAI (r=0.294, P=0.004; r=-0.312, P=0.002; and r=-0.382, P<0.001, resp.). ICAM-1 level showed no significant correlation with SLEDAI (P=0.062). There were significant correlations of VCAM-1 and anti-C1q antibody with anti-dsDNA (r=0.226, P=0.006 and r=0.511, P<0.001, resp.). VCAM-1 showed poor inverse correlation with serum C3 (r=-0.183, P=0.028) and fair inverse correlation with serum C4 (r=-0.251, P=0.002). Anti-C1q antibody demonstrated fair inverse correlation with both sera C3 and C4 (r=-0.420, P≤0.001 and r=-0.398, P<0.001, resp.). However, ICAM-1 showed no significant correlation with anti-dsDNA and sera C3 and C4 (P=0.259, P=0.626 and P=0.338, resp.). Conclusions. The serum levels of anti-C1q antibody in SLE patients showed the best correlation with the SLEDAI and standard immunological tests for SLE disease activity. These data support that anti-C1q antibody is a useful marker for monitoring SLE global disease activity. The potential of VCAM-1 needs further confirmation.

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Association of Vitamin D Status With Liver and Kidney Disease: A Systematic Review of Clinical Trials, and Cross-Sectional and Cohort Studies

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000540 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Seyed Mostafa Parizadeh ◽

Majid Rezayi ◽

Reza Jafarzadeh-Esfehani ◽

Amir Avan ◽

Hamideh Ghazizadeh ◽

...

Keyword(s):

Vitamin D ◽

Kidney Disease ◽

Renal Disease ◽

Cohort Studies ◽

Cochrane Library ◽

Major Public Health Problem ◽

Vitamin D Status ◽

Cross Sectional ◽

Beneficial Effects ◽

Vitamin D Levels

Abstract. Background: Vitamin D deficiency (VDD) is a major public health problem. There are few comprehensive systematic reviews about the relationship between Vitamin D status and liver and renal disease in Iran. Methods: We systemically searched the following databases: Web of Science; PubMed; Cochrane Library; Scopus; Science Direct; Google Scholar and two Iranian databases (Scientific Information Database (SID) and IranMedex) up until November 2017 to identify all randomized control trials (RCTs), case control, cross-sectional and cohort studies investigating the association between vitamin D and any form of liver or kidney disease. Results: Vitamin D insufficiency, or deficiency (VDD), is highly prevalent in Iran, reports varying between 44.4% in Isfahan to 98% in Gorgan. There is also a high prevalence of VDD among patients with liver or kidney disease, and the administration of vitamin D supplements may have beneficial effects on lipid profile, blood glucose, liver function and fatty liver disease, and bone health. Low serum vitamin D levels are related with abnormalities in these laboratory and clinical parameters. Conclusion: VDD is prevalent in patients with chronic liver or renal disease in Iran. There appear to be several beneficial effects of vitamin D supplementation in vitamin D deficient patients with liver or kidney disease.

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