POST-GRAFT LOSS MONITORING OF HLA ANTIBODIES FOR RETRANSPLANTATION.

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POST-GRAFT LOSS MONITORING OF HLA ANTIBODIES FOR RETRANSPLANTATION.
David Porter Ph.D. , Shannon Maier M.S. , Cal Stone M.S. , E.N.S. Samara M.D. , Ben Cowley M.D. , Larry Pennington M.D. , Ruchi Sachdev M.D. , Greg Blakey M.D. , Grant Davis M.D. , Koushan Siami M.D. and Afzal Nikaein M.D. . Oklahoma City OK, Oklahoma University Medical Center, 73190, Pathology, Surgery and Dallas TX, Texas Medical Specialty, Inc., Transplant Laboratory .

In our center about 20% of patients awaiting renal transplant have had a prior grafts, and nearly all of these (90%) have detectable antibodies to HLA antigens or heterologous lymphocytes. In an ongoing study, we are analyzing sera from these patients to guide future donor selection and XM protocols. Criteria for inclusion in the study are: 1) loss or dysfunction of previous graft(s), 2) listing or re-listing for renal transplant, 3) no longer receiving immunosuppressive drugs (ISD). Post-ISD sera were analyzed by CDC and Flow Cytometry (FC) for anti-HLA Class I and Class II antibodies (ab). Of 48 patients, 38 (79%) had anti-Class II ab by FC versus 35(73%) having anti-Class I. By T-cell CDC, 31(64%) were positive. In 3 cases (6%), a classical 0% PRA by CDC and negative Class I by FC were found to be positive for Class II ab by FC. Antibody specificities to donor Class I were indicated for 18 patients. Additional specificities could be uncovered by dilution studies using CDC PRA and negative pooled human sera (PHS) as diluent. In some cases, 10 fold dilutions were sufficient to unmask specificities to donor antigens of relatively high titer from high PRA (>95%) sera. The anti-HLA ab repertoire and titer just prior to graft loss(es) or in comparable patients with surviving grafts is unknown, thus no correlation to graft loss etiology is possible. However, the post-graft loss specificities detected indicate that the complete anti-HLA spectrum should be accessed in order to predict unacceptable antigens present on the next donor organ. In particular, if a positive B-cell XM is a contraindication for transplant at a given center, the presence of Class II antibodies should be determined.