2010 - TTS International Congress


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Assays to Predict Allograft Rejection

112.5 - Clinical Relevance of Pre- and Post- Transplant Alloantibodies Detected by Complement-Dependent Cytotoxicity and Luminex Methodologies in Liver Transplantation

Presenter: Maria Cristina, Ribeiro de Castro, Sao Paulo, Afghanistan
Authors: Monteiro F., Rodrigues H., Kalil-Filho J., Adams P., Paredes M., Massarolo P., Mies S., Ribeiro de Castro M.

CLINICAL RELEVANCE OF PRE- AND POST- TRANSPLANT ALLOANTIBODIES DETECTED BY COMPLEMENT-DEPENDENT CYTOTOXICITY AND LUMINEX METHODOLOGIES IN LIVER TRANSPLANTATION

ASSAYS TO PREDICT ALLOGRAFT REJECTION

F. Monteiro1, H. Rodrigues1, J.E. Kalil-filho1, P. Adams2, M. Paredes3, P. Massarolo3, S. Mies3, M.C. Ribeiro de castro1
1Medical School, University Of Sao Paulo, Laboratory of Transplantation Immunology, Sao Paulo/BRAZIL, 2Ohio State University Medical Center, Clinical Histocompatibility Laboratory, Columbus/UNITED STATES OF AMERICA, 3University Of São Paulo, Medical School São Paulo, Liver Unit, Sao Paulo/BRAZIL

Body: While HLA sensitization has been shown to represent a significant risk factor in kidney transplant, it is not yet clear if this holdstrue for liver transplantation. The objectives of this study were 1) to analyze liver recipients for the presence of alloantibodies using CDC and Luminex assays, and 2) to determine when and if thissensitization poses a risk to the liver allograft. To do this, a retrospective analysis of sera from 112 deceased liver graft transplants performed between October/98 and June/00 was undertaken. Onlypatients with at least 2 samples collected after the transplant were included in this study (15 patients were excluded). A total of 518 serum specimens were analyzed. HLA antibody screening wasperformed by both CDC and Luminex assay (Tepnel Lifecodes Corporations). For both assays, a %PRA of equal or greater than 10% was considered positive. Donor specific antibodies (DSA) against HLAclass I and class II donor antigens were detected by the Luminex assay. The agreement between T and B cell CDC and Luminex assays were 67% and 77% for pre- and post-transplant specimen comparison,respectively. Graft dysfunction, i.e., transplant failure or rejection episodes, was not associated with both positive pre-transplant CDC or Luminex PRA values. Likewise, positive posttransplant Tcell or B cell CDC PRA value were not associated with graft dysfunction. In contrast, Luminex PRA values detected within the first year posttransplant were significantly higher in patients (33/49,67.3%) who had graft dysfunction when compared with PRA values from patients (21/48, 43.8%) with good outcomes (P = 0.017). In addition, this correlation was lost when this analysis was carried outexclusively with anti-MHC Class I antibodies, but it was sustained in an analysis limited to anti- HLA Class II antibodies. The frequency of posttransplant anti-donor HLA class I or class II detectedby the Luminex assay was 32.2% (10 patients with pre-transplanted DSA were excluded). Patients with graft dysfunction within 3 months (14/30, 46.7%) displayed 2 times more DSA than patients with goodoutcome (14/57, 24.6%, P = 0.021). Finally, when patients lost all DSA during the first six months, follow-up testing demonstrated significantly better graft survival than patients whose DSApersisted(16/20, 80.0% vs. 5/8, 62.5%, respectively, P = 0.044). In conclusion, the findings presented here reveal that pre- and posttransplant monitoring of HLA antibodies with Luminex methodologyallows the identification of high-risk patients with poor graft outcomes.

Disclosure: All authors have declared no conflicts of interest.


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