Glomerular membrane attack complex is not a reliable marker of ongoing C5 activation in lupus nephritis.
Adolescent
Adult
Aged
Biomarkers
/ analysis
Biopsy
Complement Activation
Complement C5
/ antagonists & inhibitors
Complement Membrane Attack Complex
/ analysis
Female
Humans
Immunosuppressive Agents
/ pharmacology
Kidney Glomerulus
/ immunology
Lupus Nephritis
/ drug therapy
Male
Middle Aged
Patient Selection
Reproducibility of Results
Retrospective Studies
Young Adult
complement
glomerulonephritis
renal pathology
systemic lupus erythematosus
Journal
Kidney international
ISSN: 1523-1755
Titre abrégé: Kidney Int
Pays: United States
ID NLM: 0323470
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
02
05
2018
revised:
26
09
2018
accepted:
27
09
2018
pubmed:
19
1
2019
medline:
15
2
2020
entrez:
19
1
2019
Statut:
ppublish
Résumé
Complement plays an important role in the pathogenesis of lupus nephritis (LN). With the emergence of therapeutic complement inhibition, there is a need to identify patients in whom complement-driven inflammation is a major cause of kidney injury in LN. Clinical and histopathological data were obtained retrospectively from 57 biopsies with class III, IV, and V LN. Biopsies were stained for complement components C9, C5b-9, C3c, and C3d and for the macrophage marker CD68. C9 and C5b-9 staining were highly correlated (r = 0.92 in the capillary wall). C5b-9 staining was detected in the mesangium and/or capillary wall of both active and chronic proliferative LN in all but one biopsy and in the capillary wall of class V LN in all biopsies. C5b-9 staining intensity in the tubular basement membrane correlated with markers of tubulointerstitial damage, and more intense capillary wall C5b-9 staining was significantly associated with nonresponse to conventional treatment. Glomerular C5b-9 staining intensity did not differ between active and chronic disease; in contrast, C3c and CD68 staining were associated with active disease. Evaluation of serial biopsies and comparison of staining in active and chronic LN demonstrated that C5b-9 staining persisted for months to years. These results suggest that C5b-9 staining is almost always present in LN, resolves slowly, and is not a reliable marker of ongoing glomerular C5 activation. This limits the utility of C5b-9 staining to identify patients who are most likely to benefit from C5 inhibition.
Identifiants
pubmed: 30655025
pii: S0085-2538(18)30789-0
doi: 10.1016/j.kint.2018.09.027
pmc: PMC6389546
pii:
doi:
Substances chimiques
Biomarkers
0
Complement C5
0
Complement Membrane Attack Complex
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
655-665Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
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