#37
ACUTE AND HYPERACUTE VASCULAR REJECTION INDUCED BY XENOGENEIC ANTI-HUMAN THYMOCYTE ANTIBODIES.
Adriana I. Colovai, PhD, Rodica E. Vasilescu, MD, Aurica Foca-Rodi, MD, Glen S. Markowitz, MD, Vivette D. D
Agati, MD, Raffaello Cortesini, MD and Nicole Suciu-Foca, PhD. New York NY, USA, Columbia Univ., 10032, Pathology.
Xenogeneic anti-human thymocyte immunoglobulins (ATG) have been used in renal transplantation for prevention and treatment of acute rejection. Several studies have described the beneficial effect and the safety of rabbit-derived Thymoglobulin and equine ATGAM. We now report on two cases in which treatment with Thymoglobulin and ATGAM induced hyperacute and acute vascular rejection, respectively. Pre-transplant immunologic evaluation of the two patients indicated that anti-donor antibodies were absent in the patients’ sera. Complement dependent cytotoxicity, ELISA, FlowPRA and Luminex assays indicated the absence of any anti-HLA antibodies. Notably, flow cytometry crossmatch using endothelial cells (EC) was also negative. Induction therapy with ATG was initiated for each of the two patients at the time of transplantation. Sera obtained at the time of the surgery and thereafter were tested for human and xenogeneic anti-lymphocytic and -EC antibodies. While alloantibodies remained undetectable for 30 days post-transplant, xenogeneic antibodies that strongly bound to human lymphocytes and EC, were identified in the sera obtained up to 20 days post-transplantation and treatment with ATG. Hence, our results indicate that the xenospecific immunoglobulins that were used for treatment contained anti-lymphocytic and -EC antibodies with devastating effects on the graft. Moreover, the patient who experienced hyperacute rejection and required transplant nephrectomy within 24 hr developed anti-donor HLA class II antibodies at 3 months post-surgery. Such adverse effects can only be avoided by testing xenospecific immunoglobulins for binding to human EC, and excluding the lots that contain anti-EC antibodies.