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DESENSITIZATION PROTOCOLS FOR PATIENTS WITH DONOR-SPECIFIC-ANTIBODIES: HOW LOW SHOULD WE GO (TITER)?.
M. Buckingham , J. Leventhal , J. Friedewald , M. Abecassis and A.R. Tambur . 1 Surg, Northwestern University, Chicago, IL, USA .
Sensitization to human leukocyte antigens, with resultant donor specific antibodies (DSA), is particularly frustrating for pts who have a live donor (LD), as their waiting time could be extremely short were it not for the positive crossmatch. We have used a strategy to desensitize LD renal transplant recipients that integrates therapies to disrupt memory-dependent antibody responses by purging both T helper and B cells (Rituxan and Campath 1H). Consecutive daily PP followed by IVIg (0.2mg/kg) was performed 3-4/week of transplant. Maintenance therapy consisted of Tacrolimus and Cellcept.
Immunologic parameters of 6 pts undergoing desensitization are shown below. DSA titer was determined before, during, and after desensitization protocols using single-antigen (high definition) flow cytometry based analysis. The decision to transplant was based on substantial reduction, but not necessarily complete elimination, of DSA. Importantly, DSA titers were monitored post transplant to ensure early detection of rise in antibody production. Elevation of DSA titers was treated by additional PP/IVIg cycles, until titers were substantially reduced again. No pts experienced antibody-mediated rejection, and all continue to enjoy excellent allograft function. We conclude that consistent monitoring of DSA titers is indicative of the patientsresponsiveness to desensitization protocols. Further, it is crucial for early detection of
creeping
increase in DSA titer, requiring additional PP/IVIg cycles.
DSA specificity DSA titer pre-Rx DSA titer pre-Tx DSA titer (post-TX) Current sCr (mg/dL) B18 1:256 1:16 Neg (3Y) 1.4 B8; DR7 1:256 1:32 1:64 (8M) 1.7 B27 1:32 Neg Neg (6M) 1.0 DQ5 1:256 1:8 1:64 (7M) 0.7 DR1 1:256 1:8 1:2 (6W) 1.0 DRB1*0405 1:32 1:8 1:4 (4W) 1.4