Back to Search
Start Over
A central role of plasmin in cardiac injury initiated by fetal exposure to maternal anti-Ro autoantibodies.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2013 Aug; Vol. 52 (8), pp. 1448-53. Date of Electronic Publication: 2013 Apr 18. - Publication Year :
- 2013
-
Abstract
- Objective: Cardiac neonatal lupus (cardiac-NL), initiated by surface binding of anti-Ro60 autoantibodies to apoptotic cardiocytes during development, activates the urokinase plasminogen activator/urokinase plasminogen activator receptor (uPA/uPAR) system. Subsequent accumulation of apoptotic cells and plasmin generation facilitates increased binding of anti-Ro60 by disrupting and cleaving circulating β2-glycoprotein I (β2GPI) thereby eliminating its protective effect. The association of soluble levels of components of the uPA/uPAR system with cardiac-NL was examined.<br />Methods: Levels of the uPA/uPAR system were assessed by ELISA in cord blood and immunohistological evaluation of autopsies.<br />Results: uPA, uPAR and plasminogen levels were each significantly higher in cord blood from cardiac-NL (n = 35) compared with non-cardiac-NL (n = 26) anti-Ro-exposed neonates: 3.3 ± 0.1 vs 1.9 ± 0.05 ng/ml (P < 0.0001), 6.6 ± 0.3 vs 2.1 ± 0.2 ng/ml (P < 0.0001) and 435 ± 34 vs 220 ± 19 ng/ml (P < 0.0001), respectively. In three twin pairs discordant for cardiac-NL, the twin with cardiac-NL had higher levels of uPA, uPAR and plasminogen than the unaffected twin (3.1 ± 0.1 vs 1.9 ± 0.05 ng/ml; P = 0.0086, 6.2 ± 1.4 vs 2.2 ± 0.7 ng/ml; P = 0.147 and 412 ± 61 vs 260 ± 27 ng/ml; P = 0.152, respectively). Immunohistological evaluation of three hearts from fetuses dying with cardiac-NL revealed macrophages and giant cells expressing uPA and plasminogen in the septal region.<br />Conclusion: Increased soluble uPA, uPAR and plasminogen in cord blood and expression in affected tissue of fetuses with cardiac-NL supports the hypothesis that fetal cardiac injury is in part mediated by plasmin generation initiated by anti-Ro binding to the apoptotic cardiocyte.
- Subjects :
- Antibodies, Antinuclear immunology
Antibodies, Antinuclear metabolism
Biomarkers
Case-Control Studies
Enzyme-Linked Immunosorbent Assay
Female
Fibrinolysin metabolism
Heart Diseases mortality
Heart Diseases pathology
Humans
Immunohistochemistry
Infant, Newborn
Lupus Erythematosus, Systemic immunology
Lupus Erythematosus, Systemic mortality
Lupus Erythematosus, Systemic pathology
Macrophages immunology
Myocytes, Cardiac immunology
Myocytes, Cardiac metabolism
Pregnancy
Receptors, Urokinase Plasminogen Activator blood
Reference Values
Ribonucleoproteins metabolism
Survival Rate
Urokinase-Type Plasminogen Activator blood
Urokinase-Type Plasminogen Activator immunology
Fetal Blood immunology
Fibrinolysin immunology
Heart Diseases immunology
Lupus Erythematosus, Systemic congenital
Receptors, Urokinase Plasminogen Activator immunology
Ribonucleoproteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 52
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 23598443
- Full Text :
- https://doi.org/10.1093/rheumatology/ket156