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Combined Antagonism of Early Inflammatory Pathways Does Not Prevent Acute Rejection in Vascularized Composite Allotransplantation (VCA)
Majid Rezaei, Carlos Ordenana, Vahe Fahradyan, Payam Sadeghi, Robert Fairchild, William Baldwin, Danielle Kish, Frank Papay, Antonio Rampazzo, Bahar Bassiri Gharb
Cleveland Clinic Foundation
2020-02-04
Presenter: Payam Sadeghi, M.D.
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting. The program director is responsible for making a statement within the confines of the box below specific to how much of the work on this project represents the original work of the resident. All authors/submitters of each abstract should discuss this with their respective program director for accurate submission of information as well as the program director's approval for inclusion of his/her electronic signature.
Director Name: Bahar Bassiri Gharb
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Purpose: Immunosuppression is associated with serious adverse effects. Anti-Tumor Necrosis Factor á (TNF- á), anti-CD40 Ligand antibody and Lymphocyte Function Associated Antigen 1 (LFA-1) antagonism have shown to prolong the survival of heart allografts up to 100 days. This study aimed to characterize the efficacy of combined antibody suppression in preventing acute rejection in a rat hindlimb transplant model.
Methods: Twelve hindlimb transplants were performed from ACI donors to Lewis recipients. Animals in control group (n=6) received Tacrolimus (1mg/kg), Mycophenolate (20mg/kg) and Steroid (0.5mg/kg) daily for 100 days. In the experimental group (n=6), Anti-LFA1 (10mg/kg) was given one day preoperatively. On transplantation day, anti-TNF (10mg/kg) and anti-CD40L (16mg/kg) were administered. On post-operative day 1, all three antibodies were given. Animals were assessed for survival, clinical and histological signs of rejection .
Results: The survival rate for the control group was 81±27 days. Three animals died for failure to thrive and development of gastrointestinal tumors at 62±28.9 days post-operatively. In the experimental group, all animals presented acute rejection of the allograft within 8±2 days. The survival rates of the 2 groups were significantly different (p<0.001). Skin samples in control group displayed mild inflammation, and grade IV rejection in the experimental group.
Conclusions: Combined Antagonism of early inflammatory pathways alone does not prevent acute rejection in this model. This strategy does not seem strong enough to prevent the immediate response of the immune system. The efficacy of the combined antibody treatment following induction with conventional agents has yet to be investigated.
