SPECIFIC DOWN–REGULATION OF ANTIBODY TO DONOR HLA IN RENAL TRANSPLANTATION

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TITLE: SPECIFIC DOWN–REGULATION OF ANTIBODY TO DONOR HLA IN RENAL TRANSPLANTATION

Dessislava Kopchaliiska,¹ Mary S Leffell,¹ Robert A. Montgomery,² Milagros Samaniego,¹ Alicia Neu,¹ Andrea A. Zachary.¹

¹Department of Medicine, Johns Hopkins University, Baltimore, MD; ²Surgery, Johns Hopkins University, Baltimore, MD

Antibody to donor HLA antigens, present at the time of or developing after renal transplantation, represents a substantial risk for antibody–mediated rejection. We have used a treatment protocol comprised of plasmapheresis and low dose hyperimmune globulin (CytoGam®, MedImmune, Inc.) to achieve a durable suppression of antibody to donor but not, necessarily, third party HLA. The treatment was applied to 21 patients with donor–specific antibody present prior to transplantation and 7 patients who experienced antibody–mediated rejection after transplantation. Antibody to third party HLA was also present in 23 of the 28 patients. ELISA and cytotoxicity antibody screens, cytotoxicity and flow cytometric crossmatches, and antigen–specific absorption or blocking were used to characterize recipient serum reactivity. The specificities of antibodies were for class I antigens , class II antigens , or both in 11, 8, and 9 patients, respectively. During treatment, both donor–specific and third party–specific antibodies showed stepwise reduction. At the end of the treatment, loss of donor–specific antibody was observed in 24 of 28 patients. In contrast antibody to third party was eliminated in only 5 of 23 patients (p < 0.001). In patients that could be followed beyond the end of treatment, we saw that donor–specific antibodies remained undetectable in 16 of 18 patients, compared to only 2 of 14 patients with a persistant loss of antibody to third party antigens (p < 0.0001). We have begun to investigate various mechanisms that might account for these observation, such as the development of anti–idiotypic antibody. In two patients tested thus far, some post–treatment sera lacking anti–donor antibody were able to block sera with anti–donor reactivity while pre–treatment sera negative for anti–donor HLA antibody did not. All samples were absorbed with W6/32 coated beads to remove soluble donor HLA. Therefore, the most likely cause of the inhibition of donor reactivity is the present of anti–idiotypic antibody. In both patients, antibody to third party HLA was present in the post–treatment sera.