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Anti-plasminogen antibodies compromise fibrinolysis and associate with renal histology in ANCA-associated vasculitis.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2010 Dec; Vol. 21 (12), pp. 2169-79. Date of Electronic Publication: 2010 Sep 16. - Publication Year :
- 2010
-
Abstract
- Antibodies recognizing plasminogen, a key component of the fibrinolytic system, associate with venous thrombotic events in PR3-ANCA vasculitis. Here, we investigated the prevalence and function of anti-plasminogen antibodies in independent UK and Dutch cohorts of patients with ANCA-associated vasculitis (AAV). We screened Ig isolated from patients (AAV-IgG) and healthy controls by ELISA. Eighteen of 74 (24%) UK and 10/38 (26%) Dutch patients with AAV had anti-plasminogen antibodies compared with 0/50 and 1/61 (2%) of controls. We detected anti-plasminogen antibodies in both PR3-ANCA- and MPO-ANCA-positive patients. In addition, we identified anti-tissue plasminogen activator (tPA) antibodies in 13/74 (18%) patients, and these antibodies were more common among patients with anti-plasminogen antibodies (P = 0.011). Eighteen of 74 AAV-IgG (but no control IgG) retarded fibrinolysis in vitro, and this associated with anti-plasminogen and/or anti-tPA antibody positivity. Only 4/18 AAV-IgG retarded fibrinolysis without harboring these antibodies; dual-positive samples retarded fibrinolysis to the greatest extent. Patients with anti-plasminogen antibodies had significantly higher percentages of glomeruli with fibrinoid necrosis (P < 0.05) and cellular crescents (P < 0.001) and had more severely reduced renal function than patients without these antibodies. In conclusion, anti-plasminogen and anti-tPA antibodies occur in AAV and associate with functional inhibition of fibrinolysis in vitro. Seropositivity for anti-plasminogen antibodies correlates with hallmark renal histologic lesions and reduced renal function. Conceivably, therapies that enhance fibrinolysis might benefit a subset of AAV patients.
- Subjects :
- Analysis of Variance
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis metabolism
Antibodies, Anti-Idiotypic metabolism
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Female
Humans
Immunoglobulin G analysis
Kidney Diseases immunology
Kidney Function Tests
Male
Netherlands
Plasminogen metabolism
Reference Values
Statistics, Nonparametric
United Kingdom
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis immunology
Antibodies, Anti-Idiotypic immunology
Antibodies, Antineutrophil Cytoplasmic immunology
Fibrinolysis immunology
Kidney Diseases pathology
Plasminogen immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 21
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 20847144
- Full Text :
- https://doi.org/10.1681/ASN.2010030274