Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus

Enocsson, Helena; Wetterö, Jonas; Skogh, Thomas; Sjöwall, Christopher

doi:10.1016/j.trsl.2013.07.003

Cited by 48 publications

(55 citation statements)

References 53 publications

(55 reference statements)

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“…This study comprised 198 patients with established SLE of which 19 were followed consecutively. Serum suPAR was not related to any disease activity measures, neither at a cross-sectional analysis, nor at an individual level in patients followed consecutively, and was not found to differ significantly from the levels found in 100 healthy controls [1,14].…”

Section: Supar As a Biomarker In Sle And Other Rheumatic Diseasescontrasting

confidence: 57%

“…However, we found no associations between serum C3 or C4 and suPAR levels in our cohort [1]. Furthermore the uPAR binding partner vitronectin [3,32], which has been detected in complement and immune complex deposits of proliferative nephritis [105], is a regulator of the terminal complement pathway by binding C5b-9 [106].…”

Section: The Complement Systemmentioning

confidence: 75%

“…There are also observations on involvement of the uPAR system in systemic sclerosis [91][92][93] and Behçet's disease [94]. The first report on suPAR in SLE was presented by us as an abstract at the 2011 meeting of the American Colleague of Rheumatology [1,14]. This study comprised 198 patients with established SLE of which 19 were followed consecutively.…”

Section: Supar As a Biomarker In Sle And Other Rheumatic Diseasesmentioning

confidence: 99%

“…The soluble form of the urokinase plasminogen activator receptor (uPAR/CD87) was recently evaluated as a serum biomarker in systemic lupus erythematosus (SLE), and elevated levels were found to correlate strongly with irreversible organ damage [1]. uPAR is a multi-ligand receptor, expressed on several cell types, and the receptor is involved in proteolysis, cell migration, angiogenesis and inflammation [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Later, a substantial prognostic value of suPAR was demonstrated for infectious diseases such as HIV, tuberculosis, sepsis [5] and malaria [6][7][8][9]. Until today, suPAR has been evaluated as a biomarker of inflammation, organ damage and clinical outcome in numerous disorders including cardiovascular disease, hepatitis, renal disorders and rheumatic diseases [2,[10][11][12][13] but it was only recently studied in SLE [1,14], a disease where reliable biomarkers of disease activity and organ damage are highly warranted [15].…”

Section: Introductionmentioning

confidence: 99%

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Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Enocsson¹,

Sjöwall²,

Wetterö³

2015

Clinica Chimica Acta

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The expression of uPAR is mainly regulated by growth factors and pro-inflammatory cytokines like basic fibroblast growth factor, epidermal growth factor, tumor necrosis factor, interleukin ( suPAR as a clinical marker of inflammation and organ damagePlasma membrane expression of uPAR as well as the levels of circulating suPAR have been investigated in relation to a broad range of conditions and suPAR has been referred to as a "molecular crystal ball" due to its prognostic value in diseases like tuberculosis, HIV, sepsis and cancer [2,6,13,26,58,59]. Further, it has been reported that it reflects overall immune activation and systemic inflammation [2]. suPAR has also emerged as a potential biomarker of fibrosis in chronic liver diseases of diverse etiology [10,11,[60][61][62].Recently, suPAR attracted significant attention in primary focal segmental glomerulosclerosis (FSGS). data from this pilot study revealed significantly higher suPAR levels among patients with moderately or highly elevated SDI after study inclusion, compared to patients without SDI increase (Figure 2).Furthermore, there were higher death rates among patients in the two groups with SDI increase (Figure 2). However, it is well known that present organ damage predicts further organ damage [17,100], and thus, adjustment for SDI at baseline should be performed to reduce the risk of bias. A stepwise linear multiple regression analysis was therefore performed to evaluate the impact of suPAR on future SDI increase. After adjusting for age, sex and SDI at study inclusion, we found suPAR levels to have a significant impact on future SDI increase (p = 0.005, standardized β = 0.20) whereas SDI at study inclusion was excluded from the model. Since recent studies have revealed an inverse correlation between serum suPAR and glomerular filtration [67,68,96], we also included estimated glomerular filtration (eGFR) (calculated by the 4-variable Modification of Diet in Renal Disease StudyGroup formula [101]) in the analysis, but eGFR was not retained in the model. From these results, we suggest that suPAR can actually predict organ damage independent of present SDI score or eGFR, but that a prospective study examining the association between suPAR levels at the time of diagnosis with future SDI would be preferable.In line with these findings, elevated suPAR levels have previously been demonstrated to associate with the risk of developing cancer, cardiovascular disease and type 2 diabetes later in life in the general population [7]. Importantly, these associations were independent of CRP, which is known for its predictive value in cardiovascular disease [7,102].7 Potential roles of suPAR in SLE pathogenesisAssessment of circulating suPAR levels at the clinical laboratory could possibly become a future way to estimate organ damage in SLE, and suPAR would be an even more appealing biomarker candidate if the levels could be mechanistically linked to the disease. The pathogenesis of SLE is notoriously complex and not fully understood, but includes disturbances in t...

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Section: Supar As a Biomarker In Sle And Other Rheumatic Diseasescontrasting

confidence: 57%

Section: The Complement Systemmentioning

confidence: 75%

Section: Supar As a Biomarker In Sle And Other Rheumatic Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Enocsson¹,

Sjöwall²,

Wetterö³

2015

Clinica Chimica Acta

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Association of Serum C‐Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon‐α and a C‐Reactive Protein Gene Variant

Enocsson

Sjöwall

Kastbom

et al. 2014

Arthritis & Rheumatology

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Objective. The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE).We previously demonstrated an inhibitory effect of IFN␣ on interleukin-6 (IL-6)-induced C-reactive protein (CRP) in vitro, hypothetically explaining the poor correlation between disease activity and CRP levels in SLE. This study was undertaken to investigate disease activity, IL-6 levels, and CRP levels in relation to a CRP gene polymorphism and IFN␣.Methods. Sera from 155 SLE patients and 100 controls were analyzed for CRP. Patients were genotyped for a CRP single-nucleotide polymorphism (rs1205) associated with low CRP levels. Serum IFN␣ and IL-6 levels were quantified by immunoassays. Clinical disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K).Results. CRP levels were increased in SLE patients compared to controls, but were not associated with SLEDAI-2K or IL-6 levels. However, exclusion of patients carrying at least one rs1205 minor allele revealed an association between disease activity and CRP levels (P ‫؍‬ 0.005). We found a strong association between disease activity and CRP levels (P < 0.0005) when patients with measurable IFN␣ levels as well as the minor allele of rs1205 were excluded from the analysis. Similarly, when patients with elevated IFN␣ levels and/or the rs1205 polymorphism were excluded, IL-6 levels were associated with CRP levels. Conclusion. The present study demonstrates that the serum IFN␣ level as well as the CRP genotype affect the CRP response in SLE patients. Lack of correlation between serum levels of CRP and disease activity could therefore be explained by activation of the type I IFN system and polymorphisms in the CRP gene.

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Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Rasmussen

Schultz

Gaardsting

et al. 2017

Intl Journal of Cancer

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In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin‐3, mannose‐binding lectin, ficolin‐1, ficolin‐2 and ficolin‐3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C‐reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow‐up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self‐reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin‐1‐3, MBL and pentraxin‐3 were not associated with cancer.

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Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus

Cited by 48 publications

References 53 publications

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Soluble urokinase plasminogen activator receptor—A valuable biomarker in systemic lupus erythematosus?

Association of Serum C‐Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon‐α and a C‐Reactive Protein Gene Variant

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

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