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Article first published online: 27 JUN 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 17, Issue 7, pages 779–788, July 2011
How to Cite
Aguilera, I., Sousa, J. M., Gavilan, F., Gomez, L., Álvarez-Márquez, A. and Núñez-Roldán, A. (2011), Complement component 4d immunostaining in liver allografts of patients with de novo immune hepatitis. Liver Transpl, 17: 779–788. doi: 10.1002/lt.22302
This study was supported by the Spanish Ministry of Health and Consumers through the Health Research Fund (grants 05/0733 and 05/0374), by the Andalusian Autonomous Government (grants PI-0332/2007 and P07-CTS-02886), and by the European Community through the European Regional Development Fund. Isabel Aguilera is a researcher from the Carlos III Institute of Health (I3 National Health System (SNS) Program, Progress and Health Foundation, Andalusian Autonomous Government).
See Editorial on Page 747
- Issue published online: 27 JUN 2011
- Article first published online: 27 JUN 2011
- Accepted manuscript online: 21 MAR 2011 12:21PM EST
- Manuscript Accepted: 6 MAR 2011
- Manuscript Received: 11 NOV 2010
De novo immune hepatitis (DNIH) is a form of late graft dysfunction after liver transplantation. The fine mechanisms leading to the development of DNIH are not known, and whether this hepatitis is a form of rejection or a result of an auto/alloimmune injury has not been established. In our patients, DNIH was always preceded by the production of donor-specific antibodies against the glutathione S-transferase T1 (GSTT1) enzyme because of a genetic mismatch in which the donors carried the wild-type gene and the recipients displayed the null genotype. Complement component 4d (C4d) immunopositivity in 12 paraffin-embedded liver biopsy samples from 8 patients diagnosed with DNIH associated with anti-GSTT1 antibodies was retrospectively evaluated. Six patients with a diagnosis of chronic rejection (CR) and 7 patients with hepatitis C virus recurrence were included as control groups. Among the patients with DNIH, 7 showed C4d-positive immunostaining localized in the portal tracts, whereas in the tested biopsy samples of the 2 control groups, this staining pattern was absent. Four biopsy samples of the CR group showed C4d-positive sinusoidal staining. This study confirms the activation of the complement pathway in the presence of donor-specific antibodies, which was shown by the deposition of C4d elements in liver biopsy samples of patients with DNIH. The use of C4d as a marker of antibody-mediated rejection in liver allografts in the presence of antidonor antibodies is discussed, and it may contribute to improved differential diagnoses based on biopsy findings. Liver Transpl 17:779-788, 2011. © 2011 AASLD.