| Autor: |
Berden AE; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands., Nolan SL, Morris HL, Bertina RM, Erasmus DD, Hagen EC, Hayes DP, van Tilburg NH, Bruijn JA, Savage CO, Bajema IM, Hewins P |
| Jazyk: |
angličtina |
| Zdroj: |
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. |
| DOI: |
10.1681/ASN.2010030274 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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