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Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond

Barguil Macedo, Marina ; Wang, Ting ; Jönsen, Andreas LU ; Bengtsson, Anders A. LU ; Gunnarsson, Iva ; Svenungsson, Elisabet and Lood, Christian (2025) In Lupus Science and Medicine 12(1).
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antiphospholipid syndrome, lupus nephritis, systemic lupus erythematosus
in
Lupus Science and Medicine
volume
12
issue
1
article number
e001418
publisher
BMJ Publishing Group
external identifiers
  • scopus:85215401289
  • pmid:39809521
ISSN
2053-8790
DOI
10.1136/lupus-2024-001418
language
English
LU publication?
yes
id
a8474305-2599-46f0-8f96-5262ff6ba471
date added to LUP
2025-07-03 13:33:45
date last changed
2025-07-31 16:02:24
@article{a8474305-2599-46f0-8f96-5262ff6ba471,
  abstract     = {{<p>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 &lt;60 mL/min (chronic kidney disease stage 3 or more) with high accuracy, with an area under the curve of 0.92 (p&lt;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.</p>}},
  author       = {{Barguil Macedo, Marina and Wang, Ting and Jönsen, Andreas and Bengtsson, Anders A. and Gunnarsson, Iva and Svenungsson, Elisabet and Lood, Christian}},
  issn         = {{2053-8790}},
  keywords     = {{antiphospholipid syndrome; lupus nephritis; systemic lupus erythematosus}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{1}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{Lupus Science and Medicine}},
  title        = {{Neutrophil gelatinase-associated lipocalin (NGAL) in lupus nephritis and beyond}},
  url          = {{http://dx.doi.org/10.1136/lupus-2024-001418}},
  doi          = {{10.1136/lupus-2024-001418}},
  volume       = {{12}},
  year         = {{2025}},
}