Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

Xue, Jing; Yang, Jiali; Yang, Lijuan; Zhou, Shaolan; Ji, Chen; Wang, Xuemei; Yu, Nan; Liu, Xiaoming; Chi, Shuhong

doi:10.1155/2017/6861575

Cited by 20 publications

(12 citation statements)

References 59 publications

(74 reference statements)

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“…We also observed elevated levels of circulating DKK-1 in GPA patients. Despite the lack of published data on DKK-1 levels in serum of patients with vasculitis, this protein was increased in rheumatoid arthritis or systemic lupus erythematosus patients [42,43]. Moreover, in our study, serum DKK-1 levels correlated with disease activity score (BVAS) in active GPA patients, indicating that DKK-1 could be of use as a biomarker of GPA exacerbation.…”

Section: Discussioncontrasting

confidence: 58%

Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis

Surmiak

Kosałka-Węgiel

Polański

et al. 2021

Clinical and Experimental Immunology

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In vasculitis disorders, inflammation affects blood vessels. Granulomatosis with polyangiitis (GPA) is a chronic systemic vasculitis distinguished by the presence of anti-proteinase-3 autoantibodies (anti-PR3). In this study we analyzed the molecular signature of human umbilical endothelial cells (HUVECs) in response to neutrophil-derived extracellular vesicles (EVs). EVs were obtained from anti-PR3-activated neutrophils, purified and characterized by flow cytometry, nanoparticle tracking and miRNA screening. HUVECs were stimulated with EVs and miRNA/mRNA expression was measured. Cell culture media proteins were identified by antibody microarrays and selected cytokines were measured. Comparison of differentially expressed miRNAs/mRNAs between non-stimulated and EV-stimulated HUVECs revealed two regulatory patterns. Significant up-regulation of 14 mRNA transcripts (including CXCL8, DKK1, IL1RL1, ANGPT-2, THBS1 and VCAM-1) was accompanied by 11 miRNAs silencing (including miR-661, miR-664a-3p, miR-377-3p, miR-30d-5p). Significant down-regulation was observed for nine mRNA transcripts (including FASLG, CASP8, STAT3, GATA3, IRAK1 and IL6) and accompanied by up-regulation of 10 miRNAs (including miR-223-3p, miR-142-3p, miR-211-5p). Stimulated HUVECs released IL-8, Dickkopf-related protein 1 (DKK-1), soluble interleukin (IL)-1 like receptor-1 (ST2), growth differentiation factor 15 (GDF-15), angiopoietin-2, endoglin, thrombospondin-1 and vascular adhesion molecule-1 (VCAM-1). Moreover, transfection of HUVECs with mimics of highly expressed in EVs miR-223-3p or miR-142-3p, stimulated production of IL-8, ST2 and endoglin. Cytokines released by HUVECs were also elevated in blood of patients with GPA. The most increased were IL-8, DKK-1, ST2, angiopoietin-2 and IL-33. In-vitro stimulation of HUVECs by neutrophil-derived EVs recapitulates contribution of endothelium in autoimmune vasculitis. Proinflammatory phenotype of released cytokines corresponds with the regulatory network of miRNAs/mRNAs comprising both EVs miRNA and endothelial cell transcripts.

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Section: Discussioncontrasting

confidence: 58%

Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis

Surmiak

Kosałka-Węgiel

Polański

et al. 2021

Clinical and Experimental Immunology

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“…LN is a foremost risk factor for overall morbidity and mortality in SLE, and even with potent antiinflammatory and immunosuppressive therapies, it still ends in chronic kidney disease (CKD) or ESRD for many patients [12]. So, an early diagnosis of LN has an imperative clinical implication in administrative treatments of patients with SLE [13].…”

Section: Resultsmentioning

confidence: 99%

“…Clinical histories and blood samples were collected from all patients and controls, and also renal biopsies were obtained from patients with LN on the same day of blood sampling. SLE disease activity was assessed according to the SLEDAI score to mild (score, 0-10), moderate (score, [11][12][13][14][15][16][17][18][19][20], severe (score, 21-45), and very severe (score >45), with rSLEDAI consisted of four kidney-related items of the total SLEDAI: hematuria, pyuria, proteinuria, and urinary casts/high power field (HPF), and ranges from 0 (inactive renal disease) to a maximum score of 16 [9].…”

Section: Methodsmentioning

confidence: 99%

Renalase and lupus nephritis: disease activity and histopathological classification

Mahgoub

Foda

Elshambaky

et al. 2018

Egypt Rheumatol Rehabil

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Aim To measure the level of serum renalase and to clarify its relation to lupus nephritis (LN) activity and histopathological classification. Patients and methods This study was carried out on 40 patients with systemic lupus erythematosus (SLE), diagnosed according to systemic lupus international collaborating clinics classification criteria (SLICC) criteria, and 20 healthy controls. They were 20 patients without nephritis and 20 patients with LN (17 active and three inactive LN). Venous blood samples were taken from all participants for complete blood count, erythrocyte sedimentation rate, kidney function, anti-double-stranded DNA, C3, C4, and renalase level. The serum renalase levels were determined by enzyme-linked immunosorbent assay. Assessments of protein in 24-h urine collection and protein/creatinine (P/C) ratio were done. Renal biopsies were obtained from patients with LN, with staging and activity and chronicity indices assessment. SLE disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index, and LN activity was estimated by renal Systemic Lupus Erythematosus Disease Activity Index. Results Renalase levels were higher in patients with LN than both patients with SLE without LN and control group. The serum renalase levels of patients with LN were positively correlated with P/C ratio, 24-h proteinuria and C3, but negatively correlated with Systemic Lupus Erythematosus Disease Activity Index. For patients with active LN, there was no significant correlation between their serum renalase levels and the indicators of renal activity, including erythrocyte sedimentation rate, proteinuria, P/C ratio, anti-double-stranded DNA, C3, C4, and activity index of renal biopsy. The median of renalase as a marker for diagnosis of LN was 134.65, with a cutoff value of 100 μg/ml. Conclusion Serum renalase may be involved in LN pathogenesis but was not a good predictor for either LN activity or various stages of LN histopathology.

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“…Higher levels of serum and urine Dickkopf-1 (DKK-1) proteins were detected in SLE patients compared to healthy subjects. DKK-1 levels especially were higher in patients with LN in comparison to non-nephritis SLE patients ( 52 ). Urine APRIL (uAPRIL) and BAFF (uBAFF) levels were significantly increased in LN, and ROC curve examination of uBAFF and uAPRIL showed an AUC of 0.825 and 0.781, respectively, in distinguishing between nephritic and non-nephritic SLE patients ( 47 ).…”

Section: Disease Markers In Lupus Nephritismentioning

confidence: 99%

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

et al. 2022

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Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which can affect various tissues and organs, posing significant challenges for clinical diagnosis and treatment. The etiology of SLE is highly complex with contributions from environmental factors, stochastic factors as well as genetic susceptibility. The current criteria for diagnosing SLE is based primarily on a combination of clinical presentations and traditional lab testing. However, these tests have suboptimal sensitivity and specificity. They are unable to indicate disease cause or guide physicians in decision-making for treatment. Therefore, there is an urgent need to develop a more accurate and robust tool for effective clinical management and drug development in lupus patients. It is fortunate that the emerging Omics have empowered scientists in the discovery and identification of potential novel biomarkers of SLE, especially the markers from blood, urine, cerebrospinal fluids (CSF), and other bodily fluids. However, many of these markers have not been carefully validated for clinical use. In addition, it is apparent that individual biomarkers lack sensitivity or specificity. This review summarizes the sensitivity, specificity and diagnostic value of emerging biomarkers from recent studies, and discusses the potential of these markers in the development of biomarker panel based diagnostics or disease monitoring system in SLE.

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Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

Cited by 20 publications

References 59 publications

Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis

Endothelial cells response to neutrophil-derived extracellular vesicles miRNAs in anti-PR3 positive vasculitis

Renalase and lupus nephritis: disease activity and histopathological classification

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

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