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Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

ABSTRACT: Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups.Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6?months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361).The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ?6). The mean 25(OH)D level was 20.6±9.8?ng/mL. Deficiency (25(OH)D <10?ng/mL) was observed in 27 (15.9%), insufficiency (10?25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D?30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22).We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

SUBMITTER: Schoindre Y

PROVIDER: S-EPMC4213833 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

Schoindre Yoland Y Jallouli Moez M Tanguy Marie-Laure ML Ghillani Pascale P Galicier Lionel L Aumaître Olivier O Francès Camille C Le Guern Véronique V Lioté Frédéric F Smail Amar A Limal Nicolas N Perard Laurent L Desmurs-Clavel Hélène H Le Thi Huong Du D Asli Bouchra B Kahn Jean-Emmanuel JE Sailler Laurent L Ackermann Félix F Papo Thomas T Sacré Karim K Fain Olivier O Stirnemann Jérôme J Cacoub Patrice P Leroux Gaëlle G Cohen-Bittan Judith J Hulot Jean-Sébastien JS Lechat Philippe P Musset Lucile L Piette Jean-Charles JC Amoura Zahir Z Souberbielle Jean-Claude JC Costedoat-Chalumeau Nathalie N

Lupus science & medicine 20140607 1

<h4>Objectives</h4>Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting ...[more]

PMID: 25379192

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Project description:Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients. In the current study, we assessed baseline and follow-up plasma levels of 52 soluble mediators, including innate, adaptive, chemokine, and TNF superfamily members, in AA SLE patients who developed SELENA-SLEDAI defined flare 6 or 12 weeks after baseline assessment. These patients were compared to themselves during a comparable, clinically stable period (SNF, n = 18), or to demographically matched SLE patients without impending disease flare (NF, n = 13 per group). We observed significant (q < 0.05) alterations in 34 soluble mediators at baseline, with increased levels of both innate (IL-1α and type I interferons [IFN]) and adaptive cytokines (Th1-, Th2-, and Th17-type), as well as IFN-associated chemokines and soluble TNF superfamily members weeks before clinical disease flare. In contrast, stable SLE patients exhibited increased levels of the regulatory mediators IL-10 (q ≤ 0.0045) and TGF-β (q ≤ 0.0004). Because heterogeneous immune pathways were altered prior to clinical disease flare, we developed a soluble mediator score that encapsulates all mediators tested. This score is the sum of all log transformed, standardized soluble mediator levels assessed at baseline (pre-flare), weighted by their Spearman correlation coefficients for association with the SELENA-SLEDAI score at time of concurrent flare. While baseline SELENA-SLEDAI scores were similar between flare vs. NF (p = 0.7214) and SNF (p = 0.5387), the SMS was significantly higher in pre-flare SLE patients (Flare vs NF or SNF, p < 0.0001). By capturing alterations in the balance between inflammatory and regulatory mediators associated with SLE pathogenesis, the soluble mediator score approximates the immune status of SLE patients and provides a robust, predictive gauge of impending disease flare.

Project description:Systemic lupus erythematosus (SLE) is a multifaceted disease characterized by immune dysregulation and unpredictable disease activity. This study sought to evaluate the changes in plasma concentrations of soluble mediators that precede clinically defined disease flares.Fifty-two different soluble mediators, including cytokines, chemokines, and soluble receptors, were examined using validated multiplex bead-based or enzyme-linked immunosorbent assays in plasma from 28 European American patients with SLE who developed disease flare 6 or 12 weeks after a baseline assessment (preflare), 28 matched SLE patients without impending flare (nonflare), and 28 matched healthy controls. In a subset of 13 SLE patients, mediators within samples obtained preceding disease flare were compared with those within samples from the same individual obtained during a clinically stable period without flare.Compared to SLE patients with clinically stable disease, SLE patients with impending flare had significant alterations (P ? 0.01) in the levels of 27 soluble mediators at baseline; specifically, the levels of proinflammatory mediators, including Th1-, Th2-, and Th17-type cytokines, were significantly higher several weeks before clinical flare. Baseline levels of regulatory cytokines, including interleukin-10 and transforming growth factor ?, were higher in nonflare SLE patients, whereas baseline levels of soluble tumor necrosis factor receptor type I (TNFRI), TNFRII, Fas, FasL, and CD40L were significantly higher (P ? 0.002) in preflare SLE patients. The normalized and weighted combined soluble mediator score was significantly higher (P ? 0.0002) in preflare samples from SLE patients compared to samples from the same patients obtained during periods of stable disease.The levels of proinflammatory adaptive cytokines and shed TNF receptors are elevated prior to disease flare, while the levels of regulatory mediators are elevated during periods of stable disease. Alterations in the balance between inflammatory and regulatory mediators may help identify patients at risk of disease flare and help decipher the pathogenic mechanisms of SLE.

Dataset Information

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

Publications

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

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