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RESCUE FROM ACUTE VASCULAR REJECTION (AVR). ARE ALL DONOR-SPECIFIC ANTIBODIES (DSA) IMPLICATED IN HUMORAL REJECTION?
Andrew Precht, M.D., Danny Youngs, Mindy Cooper, M.D., Connie Davis, M.D., Paul Warner, Ph.D., William H. Marks, M.D.,Ph.D., Robert Wilburn, M.D., Susan Chloupek, Cydni S. Boyd, Thomas Price, M.D. and Karen A. Nelson, Ph.D.. Seattle WA, USA, Swedish Hospital and Medical Center, 99104, Organ Transplantation; Seattle WA, USA, Puget Sound Blood Center, 98104, Immunogenetics Laboratory; Seattle WA, USA, Virginia Mason Medical Center, 98111, Transplantation and Seattle WA, USA, University of Washington Medical Center, 98195, Transplant Services.
New tools to manage and to monitor for humoral rejection are increasing the frequency of transplanting highly sensitized patients. We report on a series of patients with early AVR whose rescue protocols included plasma exchange, IVIG and Rituximab. The appearance of de novo DSA in these patients was noted at the onset of AVR and levels were monitored to track efficacy of treatment. Flow cytometry crossmatch was used to identify the presence of DSA, then flow cytometry and single antigen beads were used to identify DSA specificity as well as antibody to third party antigens (epitopes not expressed by the donor). Many of these patients generated multiple DSA, and several had high titered antibodies to third party antigens. AVR was resolved in all patients in this series with a resumption of normal graft function. The drop in peak serum creatinine was coincident with removal of some DSA, but not all. DSA removed coincident with resolution were primarily directed to A locus and DR locus antigens. DSA persisting after return to graft function were primarily directed to B locus and DQ locus antigens. One hypothesis is that the level of antigen expression in the graft may play a role. Therapy with Rituximab did not remove antibody to third party antigens. There may be an active regulatory component of these rescue protocols as yet undefined.