Laminin-521 is a Novel Target of Autoantibodies Associated with Lung Hemorrhage in Anti-GBM Disease.
Adult
Aged
Animals
Anti-Glomerular Basement Membrane Disease
/ blood
Autoantibodies
/ blood
Autoantigens
/ immunology
Case-Control Studies
Collagen Type IV
/ immunology
Creatinine
/ blood
Disease Progression
Epitopes
/ immunology
Female
Hemoptysis
/ blood
Humans
Immunoglobulin G
/ blood
Kidney
/ metabolism
Kidney Failure, Chronic
/ etiology
Laminin
/ immunology
Lung
/ metabolism
Male
Mice
Middle Aged
Prognosis
Proteinuria
/ etiology
Retrospective Studies
Saimiri
Smoking
/ blood
Goodpasture’s syndrome
anti-GBM disease
autoantibodies
extracellular matrix
glomerular basement membrane
glomerulonephritis
laminin
pulmonary hemorrhage
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
08
10
2020
accepted:
28
02
2021
pubmed:
25
4
2021
medline:
21
10
2021
entrez:
24
4
2021
Statut:
ppublish
Résumé
Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known. A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity. Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%, Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.
Sections du résumé
BACKGROUND
Antiglomerular basement membrane (anti-GBM) disease is characterized by GN and often pulmonary hemorrhage, mediated by autoantibodies that typically recognize cryptic epitopes within α345(IV) collagen-a major component of the glomerular and alveolar basement membranes. Laminin-521 is another major GBM component and a proven target of pathogenic antibodies mediating GN in animal models. Whether laminin-521 is a target of autoimmunity in human anti-GBM disease is not yet known.
METHODS
A retrospective study of circulating autoantibodies from 101 patients with anti-GBM/Goodpasture's disease and 85 controls used a solid-phase immunoassay to measure IgG binding to human recombinant laminin-521 with native-like structure and activity.
RESULTS
Circulating IgG autoantibodies binding to laminin-521 were found in about one third of patients with anti-GBM antibody GN, but were not detected in healthy controls or in patients with other glomerular diseases. Autoreactivity toward laminin-521 was significantly more common in patients with anti-GBM GN and lung hemorrhage, compared with those with kidney-limited disease (51.5% versus 23.5%,
CONCLUSIONS
Besides α345(IV) collagen, laminin-521 is another major autoantigen targeted in anti-GBM disease. Autoantibodies to laminin-521 may have the potential to promote lung injury in anti-GBM disease by increasing the total amount of IgG bound to the alveolar basement membranes.
Identifiants
pubmed: 33893224
pii: 00001751-202108000-00013
doi: 10.1681/ASN.2020101431
pmc: PMC8455270
doi:
Substances chimiques
Autoantibodies
0
Autoantigens
0
Collagen Type IV
0
Epitopes
0
Immunoglobulin G
0
Laminin
0
laminin 11 protein, human
0
type IV collagen alpha3 chain
0
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1887-1897Subventions
Organisme : NIMHD NIH HHS
ID : U54 MD007586
Pays : United States
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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