A central role of plasmin in cardiac injury initiated by fetal exposure to maternal anti-Ro autoantibodies

作者：Briassouli Paraskevi^*; Halushka Marc K; Reed Joanne H; Molad Yair; Fox Talbot Karen; Buyon Lucas; Guzman Edwin; Ludomirsky Achiau; Clancy Robert M; Buyon Jill P

来源：Rheumatology, 2013, 52(8): 1448-1453.

DOI：10.1093/rheumatology/ket156

• apoptosis
• fibrosis
• inflammation

Methods. Levels of the uPA/uPAR system were assessed by ELISA in cord blood and immunohistological evaluation of autopsies.
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.
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.

• 出版日期2013-8