scholarly journals Circulating neutrophil gelatinase-associated lipocalin: a useful biomarker for assessing disease activity of ANCA-associated vasculitis

Rheumatology ◽  
2009 ◽  
Vol 48 (4) ◽  
pp. 355-358 ◽  
Author(s):  
M. Chen ◽  
F. Wang ◽  
M.-H. Zhao
Lupus ◽  
2020 ◽  
Vol 29 (4) ◽  
pp. 379-388 ◽  
Author(s):  
S Mirioglu ◽  
S Cinar ◽  
H Yazici ◽  
Y Ozluk ◽  
I Kilicaslan ◽  
...  

Objectives TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. Methods Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p < 0.001; uNGAL p = 0.002), whilst no significant differences regarding serum and urine MCP-1 levels were observed ( p = 0.189 and p = 0.106, respectively). uTWEAK ( p = 0.237), sMCP-1 ( p = 0.141), uMCP-1 ( p = 0.206), sNGAL ( p = 0.419) and uNGAL ( p = 0.443) levels did not differ between patients with active renal and extra-renal SLE. Serum TWEAK was higher in patients with active renal SLE ( p = 0.006). There were no differences between active renal SLE and active renal AAV. Levels of all biomarkers were correlated with the SLE Disease Activity Index. Conclusion sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.


2012 ◽  
Vol 39 (6) ◽  
pp. 1231-1237 ◽  
Author(s):  
ADNAN N. KIANI ◽  
TIANFU WU ◽  
HONG FANG ◽  
XIN J. ZHOU ◽  
CHUL W. AHN ◽  
...  

Objective.Vascular cell adhesion molecule-1 (VCAM-1), an adhesion molecule, is involved in the progression of glomerular and tubulointerstitial injury. Neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin superfamily, has been shown to rise in both acute and chronic kidney damage. Both VCAM-1 and NGAL have been found at high levels in the urine of patients with active lupus nephritis. We investigated both as potential biomarkers for lupus nephritis.Methods.VCAM-1 and NGAL were measured by ELISA during 1 to 8 clinic visits in 107 patients with systemic lupus erythematosus (SLE; 91% women, 51% black, 36% white, 4% Asian, 4% Hispanic, and 5% others) for a total of 190 visits. Patients’ mean age was 41 years. We analyzed the relationship between these potential urine biomarkers and the urine protein/creatinine ratio (urine Pr/Cr), the Systemic Lupus International Collaborating Clinics (SLICC) renal activity score, SLE Disease Activity Index renal descriptors, and other clinical variables.Results.VCAM-1 levels were strongly associated with the physician’s global estimate of disease activity (p = 0.0002), the renal visual analog scale (p < 0.0001), the urine Pr/Cr (p < 0.0001), and SLICC renal activity score (p < 0.0001). VCAM-1 levels were also associated with a urine Pr/Cr ≥ 0.5 (p < 0.0001). NGAL was not associated with any measure of disease activity or with lupus serologies.Conclusion.Urine VCAM-1 had a strong association with measures of disease activity, including multiple renal activity descriptors. In contrast to previous SLE studies, NGAL failed to show any association with lupus nephritis.


2015 ◽  
Vol 10 ◽  
pp. BMI.S27625 ◽  
Author(s):  
Hani Susianti ◽  
Jullyanny W. Wijaya ◽  
Ati Rastini ◽  
Kusworini Handono ◽  
Atma Gunawan ◽  
...  

Background This study was conducted to determine whether there is an association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary transforming growth factor-β1 (uTGF-β1) with lupus nephritis (LN) disease activity. Methods Urine samples from 18 LN patients were collected every month for six months then examined for uNGAL, uTGF-β1, and renal domain Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. Results The uNGAL levels were significantly different between active and inactive LN (P < 0.05). uTGF-β1 levels were not different between active and inactive LN (P > 0.05). There was a significant correlation between uNGAL levels and renal domain SLEDAI score (r= 0.417, P < 0.05). There was no correlation between uTGF-β1 levels and renal domain SLEDAI score (r = 0.031, P > 0.05). Conclusion uNGAL is better than uTGF-β1 for differentiation of active and inactive LN. uNGAL can be considered as a biomarker to monitor LN disease activity.


2017 ◽  
Author(s):  
Άρτεμις-Ωραιάνθη Κουτσονικολή

Εισαγωγή. Η νεφρίτιδα αποτελεί τον καθοριστικότερο παράγοντα της συνολικής βαρύτητας και πρόγνωσης του παιδιατρικού Συστηματικού Ερυθηματώδους Λύκου (πΣΕΛ). Η ανεύρεση νέων βιολογικών δεικτών, ειδικών για τη νεφρίτιδα του πΣΕΛ, θα επιτρέψει τη μη επεμβατική εκτίμηση της πορείας της και τη στοχευμένη θεραπεία. Τα επιστημονικά δεδομένα για τους παιδιατρικούς ασθενείς, ιδιαιτέρως για ομοιογενείς καυκάσιους πληθυσμούς, είναι ακόμη ελλειπή. Σκοπός. Να διερευνηθεί η σχέση των αντισωμάτων έναντι των νουκλεοσωμάτων (αντι-NCS) ορού, των αντισωμάτων έναντι της βασικής μεμβράνης του σπειράματος (αντι-GBM) ορού, των αντισωμάτων έναντι του παράγοντα C1q του συμπληρώματος (αντι-C1q) ορού, της πρωτεΐνης High-Mobility Group Box-1 (HMGB1) ορού και ούρων και της Neutrophil Gelatinase-Associated Lipocalin (NGAL) ούρων με: (α) την παρουσία νεφρίτιδας στον πΣΕΛ και (β) με την ενεργότητα του πΣΕΛ και της νεφρίτιδας ειδικότερα, σε έναν αμιγώς καυκάσιο πληθυσμό ασθενών από τη βόρεια Ελλάδα. Υλικό-Μέθοδοι. Ελήφθησαν δείγματα ορού και ούρων από 22 ασθενείς με πΣΕΛ και νεφρίτιδα, 20 ασθενείς με πΣΕΛ χωρίς νεφρίτιδα, 15 ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας (IgA νεφροπάθεια, νεφρίτιδα πορφύρας Henoch-Schönlein, μεταλοιμώδη νεφρίτιδα ή μεμβρανώδη σπειραματονεφρίτιδα) και 26 υγιείς μάρτυρες. Ο προσδιορισμός των βιολογικών δεικτών έγινε με τη μέθοδο ELISA. Η ενεργότητα του πΣΕΛ και της νεφρίτιδας του πΣΕΛ εκτιμήθηκε με το εργαλείο SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index-2000). Αποτελέσματα. Α. Βιολογικοί δείκτες ορού. Τα επίπεδα των αντι-NCS, των αντι-GBM, των αντι-C1q και της HMGB1 βρέθηκαν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους υγιείς μάρτυρες αλλά και συγκριτικά με τους ασθενείς με νεφρίτιδα άλλης αυτοάνοσης αιτιολογίας. Κατά τη σύγκριση των επιπέδων των βιολογικών δεικτών ορού μεταξύ των ασθενών με νεφρίτιδα του πΣΕΛ και των ασθενών με πΣΕΛ χωρίς νεφρίτιδα, τα αντι-NCS, τα αντι-GBM και η HMGB1 παρουσίαζαν στατιστικώς σημαντικά υψηλότερες τιμές στους ασθενείς με νεφρίτιδα, ενώ για τα αντι-C1q δεν παρατηρήθηκαν στατιστικώς σημαντικές διαφορές. Τα επίπεδα της HMGB1 παρουσίασαν υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Τα επίπεδα της HMGB1 και των αντι-C1q παρουσίασαν μέτρια θετική συσχέτιση με την ενεργότητα του πΣΕΛ συνολικά. Β. Βιολογικοί δείκτες ούρων. Τα επίπεδα της NGAL και της HMGB1 ήταν στατιστικώς σημαντικά υψηλότερα στους ασθενείς με νεφρίτιδα του πΣΕΛ συγκριτικά με τους ασθενείς με πΣΕΛ χωρίς νεφρίτιδα. Επιπλέον, τα επίπεδα της NGAL παρουσίασαν μέτρια θετική συσχέτιση και τα επίπεδα της HMGB1 υψηλή θετική συσχέτιση με την ενεργότητα της νεφρίτιδας του πΣΕΛ. Συμπεράσματα. Σε αυτόν τον ομοιογενή πληθυσμό Καυκάσιων ασθενών με πΣΕΛ, τα αντι-NCS, τα αντι-GBM, η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες, ενδεικτικοί της νεφρικής προσβολής. Επιπλέον, τα αντι-NCS, τα αντι-GBM και η HMGB1 ορού δεν φαίνεται να παρουσιάζουν αύξηση σε νεφρίτιδες άλλης αυτοάνοσης αιτιολογίας. Η HMGB1 ορού και ούρων και η NGAL ούρων προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας της νεφρίτιδας του πΣΕΛ. Τα αντι-C1q και η HMGB1 ορού προέκυψαν ως πιθανοί χρήσιμοι βιολογικοί δείκτες παρακολούθησης της ενεργότητας του πΣΕΛ συνολικά.


Author(s):  
Mohammed G. Flefel ◽  
Heba A. Mourad ◽  
Eiman A. Hasby ◽  
Sherif E. Ezzat ◽  
Waleed S. Mohamed

Introduction: Detection of activity of ulcerative colitis (UC) is vital for predicting treatment outcome. The assessment depends on clinical, serologic, and endoscopic findings. One of the noninvasive biomarkers for disease activity detection is serum Neutrophil Gelatinase-Associated Lipocalin (NGAL). Aim: To assess the relationship between NGAL and endoscopic, histopathologic and clinical activity of UC. Methods: This study was conducted on 50 cases with definitive diagnosis of UC and 15 cases with normal colonoscopy examination as controls. UC cases were considered active if Geobes score was ≥3.1. Complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and liver and kidney function tests were done. Serum NGAL was estimated using ELISA technique. Results: UC cases were classified into active group (n = 36) and inactive group (n = 14). In active UC cases, median value (IQR) of serum NGAL was significantly increased (101.15 (67.53 – 156.40) ng/mL) compared to inactive cases (63.35 (60.98–65.20) ng/mL) and control group (24.80 (15.50 – 31.50) ng/mL). Serum NGAL was well correlated with Geobes score, Mayo score, CRP and ESR. Serum NGAL at cut-off ≥ 63 can predict activity with sensitivity 88.89%, specificity 85.71%, PPV 94.12% and NPV 75%. Conclusion: Serum NGAL is valuable noninvasive marker for assessment of UC disease activity.


Author(s):  
Mohamed S. El Shahawy ◽  
Mahmoud H. Hemida ◽  
Hafez A. Abdel-Hafez ◽  
Tarek Z. El-Baz ◽  
Abdel-Wahab M. Lotfy ◽  
...  

2020 ◽  
Vol 31 (7) ◽  
pp. 1569-1584 ◽  
Author(s):  
Adrian Schreiber ◽  
Anthony Rousselle ◽  
Jan Klocke ◽  
Sebastian Bachmann ◽  
Suncica Popovic ◽  
...  

BackgroundNeutrophil gelatinase–associated lipocalin (NGAL) is a diagnostic marker of intrinsic kidney injury produced by damaged renal cells and by neutrophils. ANCA-associated vasculitis features necrotizing crescentic GN (NCGN), and ANCA-activated neutrophils contribute to NCGN. Whether NGAL plays a mechanistic role in ANCA-associated vasculitis is unknown.MethodsWe measured NGAL in patients with ANCA-associated vasculitis and mice with anti-myeloperoxidase (anti-MPO) antibody–induced NCGN. We compared kidney histology, neutrophil functions, T cell proliferation and polarization, renal infiltrating cells, and cytokines in wild-type and NGAL-deficient chimeric mice with anti-MPO antibody–induced NCGN. To assess the role of TH17 immunity, we transplanted irradiated MPO-immunized MPO-deficient mice with bone marrow from either wild-type or NGAL-deficient mice; we also transplanted irradiated MPO-immunized MPO/IL-17A double-deficient mice with bone marrow from either IL-17A–deficient or NGAL/IL-17A double-deficient mice.ResultsMice and patients with active ANCA-associated vasculitis demonstrated strongly increased serum and urinary NGAL levels. ANCA-stimulated neutrophils released NGAL. Mice with NGAL-deficient bone marrow developed worsened MPO-ANCA–induced NCGN. Intrinsic neutrophil functions were similar in NGAL-deficient and wild-type neutrophils, whereas T cell immunity was increased in chimeric mice with NGAL-deficient neutrophils with more renal infiltrating TH17 cells. NGAL-expressing neutrophils and CD3+ T cells were in close proximity in kidney and spleen. CD4+ T cells showed no intrinsic difference in proliferation and polarization in vitro, whereas iron siderophore–loaded NGAL suppressed TH17 polarization. We found significantly attenuated NCGN in IL-17A–deficient chimeras compared with MPO-deficient mice receiving wild-type bone marrow, as well as in NGAL/IL-17A–deficient chimeras compared with NGAL-deficient chimeras.ConclusionsOur findings support that bone marrow–derived, presumably neutrophil, NGAL protects from ANCA-induced NCGN by downregulating TH17 immunity.


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