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ANTIBODIES AGAINST DONOR HLA ANTIGENS AFTER HEART TRANSPLANTATION.
R. Vorhaben, CHS, J. Crumpton, K. Nottingham, B. Lavingia, CHS, W. S. Ring, MD, C. Yancy, MD and P. Stastny, MD. Dallas TX, UT Southwestern Med Cntr, Internal Medicine and Dallas TX, UT Southwestern Med Cntr, Surgery.

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Studies have suggested anti-HLA antibodies may play a role in acute and chronic rejection of heart allografts. We have investigated formation of HLA antibodies in 575 sera from 93 consecutive heart transplant recipients. Serum specimens were collected pre-transplant and during clinic visits at 1, 3, 6, and 12 months and with rejection, from 1996-2003. We detected antibodies by solid phase assays and single-antigen beads were used to define specificities. 11 (12%) patients were sensitized before transplant and retrospective flow crossmatches were positive in 3. With single antigen beads a reduction in fluorescence intensity was observed post-transplant with donor antigen, or antigens sharing donor epitopes suggesting antibody absorption by the graft. Post-transplant 9 (9%) non-sensitized patients developed antibodies, 4/9 (44%) donor-specific class I and class II antibodies and 5/9 (55%) only class II donor specific antibodies. Overall, after transplant we found 19 patients to have detectable HLA antibodies. 8 patients had donor-specific class I and class II antibodies, 5 patients had only anti-donor class II, 2 had anti-class I only, and 4 had no donor-specific antibodies. The average number of rejection episodes for patients without HLA antibodies and patients with no donor-specific antibody was similar, 0.12 vs. 0.00. Rejection frequency increased when donor-specific antibodies were found to class II, class I, and class I and II (1.15 p=0.025, 1.44 p=0.025, 1.63 p=0.031). Cardiovascular disease also increased in patients with anti-donor antibodies (0.16 vs. 0.42 p=0.015). Post-transplant antibodies to HLA detected with single-antigen beads appear to be associated with risk for rejection.