Premium
Oral Communication 3: Xeno Immunology – Non‐Gal Antibodies and Coagulations (1)
Author(s) -
Massimo Boldrin,
Sabrina Gavasso,
Marta Vadori,
Luca Spiezia,
Laura Cavicchioli,
Nicola Baldan,
Giulia M. De Benedictis,
Andrea Perota,
Annalisa Stefani,
Fiorella Calabrese,
Simon C. Robson,
Peter Cowan,
Cesare Galli,
Paolo Simioni,
Emanuele Cozzi
Publication year - 2013
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12060_12
Subject(s) - citation , antibody , medicine , immunology , computer science , library science
Background: Coagulative profile alterations are often associated with early occurrence of acute humoral xenograft rejection (AHXR) that occurs when pig organs are transplanted into primate. Generation of transgenic pigs for 1,3-galactosyltransferase gene-knockout (GTKO) with/without human regulatory protein (hCRP) avoided occurrence of the hyperacute rejection in pig-to-primate xenotransplantation. However, coagulation alterations such as microangiopathy and systemic consumptive coagulopathy are increasingly recognized as barriers to successful long term solid organ xenotransplantation. The aim of this study was to evaluate the traditional coagulative profile in nephrectomized cynomolgus monkeys receiving GTKO kidneys presenting additional genetic modifications.Methods: Twelve bilaterally nephrectomized cynomolgus monkeys received a kidney from different lines of GTKO pigs. Animals in Group A (n = 4) received a kidney from GTKO, CD55 donor pigs. Animals in Group B (n = 6) were transplanted with a kidney from GTKO pigs transgenic for human CD39, CD55, CD59 and fucosyltransferase (TF) proteins. Group C included animals (n = 2) xenotransplanted with a kidney from a GTKO pig transgenic for human CD55, endothelial protein C receptor (EPCR) and thrombomodulin (TM). All recipients received cyclophosphamide, cyclosporin A, mycophenolate sodium and steroids. Complete hematological and biochemical analyses were routinely performed in all xenotransplanted animals. Evaluation of platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen was performed. Clinical signs of coagulation dysregulation such as petechiae or suffusions, complete necropsy and kidney histology for the presence of fibrin were evaluated.Results: Median survival of the animals in the study was 8, 16 and 29 for Group A, B and C, respectively. All primates but one were euthanized in the presence of kidney failure. Three out of four Group A animals showed a rapid drop of platelet counts under 100,000/mm3. Four out of six Group B animals showed platelet counts between the normal range for most of the postoperative period. Group C animals showed normal platelet levels until day 20. Subsequently, both animals had a drop in platelet counts. A similar trend was also observed for hemoglobin levels, with Group C animals showing more stable levels. PT and aPTT were markedly prolonged in Group A animals; on the contrary, Group B and C animals had PT and aPTT values between the normal range.Conclusion: Preliminary data show that in animals transplanted with organs from GTKO pigs with endothelial expression of thrombomodulin and EPCR, survival is prolonged. Similarly, stable coagulation parameters appear to be associated with prolonged survival in kidney xenotransplantation. These observations suggest that control of the coagulative cascade alterations is predictive of the solid organ xenotransplantation survival