Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond
Objectives To study neutrophil gelatinase-associated lipocalin (NGAL) levels in peripheral blood in SLE, and to propose a mechanism by which neutrophils secrete NGAL on stimulation with immune complexes (IC).Methods NGAL was measured by ELISA in two independent Swedish SLE cohorts acting as explorat...
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BMJ Publishing Group
2025-01-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/12/1/e001418.full |
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| author | Elisabet Svenungsson Iva Gunnarsson Andreas Jönsen Ting Wang Anders A Bengtsson Christian Lood Marina Barguil Macedo |
| author_facet | Elisabet Svenungsson Iva Gunnarsson Andreas Jönsen Ting Wang Anders A Bengtsson Christian Lood Marina Barguil Macedo |
| author_sort | Elisabet Svenungsson |
| collection | DOAJ |
| description | Objectives To study neutrophil gelatinase-associated lipocalin (NGAL) levels in peripheral blood in SLE, and to propose a mechanism by which neutrophils secrete NGAL on stimulation with immune complexes (IC).Methods NGAL was measured by ELISA in two independent Swedish SLE cohorts acting as exploratory and validation cohort (n=124 and n=308, respectively), disease controls (n=38) and healthy controls (n=77). NGAL levels were measured in supernatant from IC-stimulated neutrophils in the presence or absence of a toll-like receptor 8 inhibitor (TLR8i).Results In the exploratory cohort, serum levels of NGAL were increased in patients with SLE as compared with healthy controls (p=0.021), and associated with histological-proven membranoproliferative lupus nephritis (LN) (p=0.018). In the validation cohort, plasma levels of NGAL were elevated in patients with a history of LN (p=0.0048), as well as in patients with SLE with secondary antiphospholipid syndrome (APS) compared with those without (p=0.0022). In both cohorts, NGAL was able to discriminate patients with a creatinine clearance <60 mL/min (chronic kidney disease stage 3 or more) with high accuracy, with an area under the curve of 0.92 (p<0.0001) and 0.94 (p=0.0088), respectively. Neutrophils stimulated with IC secrete more NGAL, when compared with baseline, and this process was blocked by adding a TLR8i.Conclusion Blood levels of NGAL are increased in patients with SLE with decreased kidney function, and in those with secondary APS. The mechanism behind NGAL increase in SLE may be related to TLR8 pathway activation by circulating RNA-containing IC. |
| format | Article |
| id | doaj-art-3c91a30b81bc4951b5893a2530a25fdc |
| institution | Kabale University |
| issn | 2053-8790 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj-art-3c91a30b81bc4951b5893a2530a25fdc2025-01-15T04:40:11ZengBMJ Publishing GroupLupus Science and Medicine2053-87902025-01-0112110.1136/lupus-2024-001418Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyondElisabet Svenungsson0Iva Gunnarsson1Andreas Jönsen2Ting Wang3Anders A Bengtsson4Christian Lood5Marina Barguil Macedo6Division of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, SwedenDivision of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, SwedenDepartment of Clinical Sciences, Rheumatology, Lund University, Lund, SwedenMedicine, University of Washington, Seattle, Washington, USADepartment of Clinical Sciences, Rheumatology, Lund University, Lund, SwedenMedicine, University of Washington, Seattle, Washington, USAMedicine, University of Washington, Seattle, Washington, USAObjectives To study neutrophil gelatinase-associated lipocalin (NGAL) levels in peripheral blood in SLE, and to propose a mechanism by which neutrophils secrete NGAL on stimulation with immune complexes (IC).Methods NGAL was measured by ELISA in two independent Swedish SLE cohorts acting as exploratory and validation cohort (n=124 and n=308, respectively), disease controls (n=38) and healthy controls (n=77). NGAL levels were measured in supernatant from IC-stimulated neutrophils in the presence or absence of a toll-like receptor 8 inhibitor (TLR8i).Results In the exploratory cohort, serum levels of NGAL were increased in patients with SLE as compared with healthy controls (p=0.021), and associated with histological-proven membranoproliferative lupus nephritis (LN) (p=0.018). In the validation cohort, plasma levels of NGAL were elevated in patients with a history of LN (p=0.0048), as well as in patients with SLE with secondary antiphospholipid syndrome (APS) compared with those without (p=0.0022). In both cohorts, NGAL was able to discriminate patients with a creatinine clearance <60 mL/min (chronic kidney disease stage 3 or more) with high accuracy, with an area under the curve of 0.92 (p<0.0001) and 0.94 (p=0.0088), respectively. Neutrophils stimulated with IC secrete more NGAL, when compared with baseline, and this process was blocked by adding a TLR8i.Conclusion Blood levels of NGAL are increased in patients with SLE with decreased kidney function, and in those with secondary APS. The mechanism behind NGAL increase in SLE may be related to TLR8 pathway activation by circulating RNA-containing IC.https://lupus.bmj.com/content/12/1/e001418.full |
| spellingShingle | Elisabet Svenungsson Iva Gunnarsson Andreas Jönsen Ting Wang Anders A Bengtsson Christian Lood Marina Barguil Macedo Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond Lupus Science and Medicine |
| title | Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond |
| title_full | Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond |
| title_fullStr | Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond |
| title_full_unstemmed | Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond |
| title_short | Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond |
| title_sort | neutrophil gelatinase associated lipocalin ngal in lupus nephritis and beyond |
| url | https://lupus.bmj.com/content/12/1/e001418.full |
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