CLINICAL RELEVANCE OF HLA ANTIBODY (SPECIFICITY AND TITER) AND DONOR SPECIFIC FLOW CYTOMETRY CROSSMATCHES IN SIROLIMUS TREATED RENAL ALLOGRAFT RECIPIENTS

Abstract

O425 Aims: We have previously suggested that renal allograft recipients with Flow PRA identified pretransplant (Tx) IgG HLA antibodies (Ab) were at significant risk for rejection and recipients with both HLA Ab and a positive (+) donor specific flow cytometry crossmatch (FCXM) experienced both rejection and graft loss. However, not all of the Ab (+), FCXM (+) grafts were lost. Methods: To understand why not all of these grafts were lost to rejection sera from Ab (+) and FCXM (+) recipients were evaluated for HLA Ab specificity and titer (strength of Ab) with results compared to rejection and graft loss. We studied 16 Sirolimus treated recipients of cadaveric donor renal allografts who were transplanted following negative IgG anti-human globulin (AHG) crossmatches (testing the most reactive historical and pre-Tx sera). Results: All 16 recipients experienced acute humoral rejections between days 7-21 post-Tx. Retrospective testing of pre-Tx sera revealed that all 16 recipients had Flow PRA identified donor specific IgG HLA Ab and donor specific FCXM reactivity. Rejections were treated with plasmapheresis and OKT-3, thymoglobulin and/or IVIG. Reversal of these acute humoral rejections was achieved in 69% (11/16) of the recipients as evidenced by a mean fall in serum creatinine (SCr) from 6.4 ± 2.9 to 1.4 ± 0.5 mg/dl. However, 31% (5/16) of the grafts were lost to rejection. To try and understand whether there were any immune differences between successful and failed grafts, we studied the pre-Tx sera from twelve of the sixteen recipients for HLA Ab titer. Pre-tx sera from four recipients who lost their grafts did not reach their end point titers until 1:256, 1:256, 1:512 and 1:1024. In contrast, pre-Tx sera from eight recipients who kept their grafts lost Ab reactivity at titers of 1:8, 1:8, 1:8, 1:8, 1:16, 1:16, 1:16 and 1:32 respectively. While all 16 recipients presented with what may be considered immune contraindications (+ donor specific IgG HLA Abs and a (+) donor specific FCXM), those patients with lower antibody titers responded to rejection therapy. Conclusions: These data suggest that the strength of Ab reactivity (Ab titer) may be important in identifying high risk recipients who may be amenable to desensitization protocols and/or therapeutic intervention resulting in prevention or successful reversal of antibody mediated rejections.