De novo HLA sensitization and antibody mediated rejection following pregnancy in a heart transplant recipient.

Here we report a case wherein both donor-specific and third-party, paternal, HLA class II specific antibodies developed following a spontaneous miscarriage resulting in antibody-mediated rejection in a patient who had undergone an orthotopic cardiac transplant six years earlier.

Sensitization following LVAD implantation using leucodepleted blood is not due to HLA antibodies.

Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitization. The objective of this study was to determine the specificity of antibodies produced by LVAD recipients using a combination of ELISA, Luminex and microcytotoxicity assays. Fifty-one LVAD patients were studied, from 44 to 838 days post-implantation. No patient developed HLA antibodies, although 24 produced IgG antibodies detectable in both ELISA and Luminex assays. These antibodies manifest as positive reactions with class I and class II wells of the ELISA and also blank wells. In Luminex assays, they produce high MFI readings with the negative control beads. Antibodies were detected 18 to 228 days after implantation. This reactivity was found to be directed against bovine serum albumin (BSA), commonly used to block non-specific binding in ELISA and Luminex assays; absorption of sera with BSA-coated beads completely abrogated reactivity in all solid phase assays, but did not eliminate anti-HLA antibodies in control sera. Ten of the 24 patients have proceeded to transplantation, with a 1-year graft survival of 69%. In conclusion, it appears that implantation of LVADS disrupts immunoregulatory pathways leading to production of anti-albumin antibodies. These can be misinterpreted as anti-HLA antibodies in solid phase assays.

The effect of panel reactive antibodies and the donor specific crossmatch on graft survival after heart and heart-lung transplantation.

Data from 699 cardiac and 290 heart-lung transplants has been analysed to determine the importance of the lymphocytotoxic crossmatch result and panel reactive antibody (PRA) status on graft survival. Donor reactive crossmatching was performed for 636 cardiac transplants. One year actuarial survival for a negative crossmatch (n = 580) was 73% compared to 56% for the positive crossmatch recipients (n = 56) p = 0.0014. Where crossmatches were performed on separated T and B cells, the T cell directed crossmatch was found to be highly predictive of graft failure in 289 cardiac transplants. One year survival for a negative crossmatch was 73% (n = 258), for B cell positive crossmatch recipients 62% (n = 24), and for a positive T cell crossmatch 28% (n = 7) (p = 0.001). Patients' PRA status were grouped into those with negative, medium and high frequencies. There was a trend (not statistically significant) for patients with PRA above 50% to have poor graft survival. Patients with PRA above 50% were significantly more likely to have a positive lymphocytotoxic crossmatch against donor lymphocytes. Donor reactive crossmatching was performed for 283 heart-lung transplants. One year actuarial survival for a negative crossmatch was 61% (n = 251) and for a positive result was 50% (n = 32), p = 0.02.(ABSTRACT TRUNCATED AT 250 WORDS)

Specificity of lymphocytotoxic antibodies formed after cardiac transplantation and correlation with rejection episodes.

Eighty-two patients have been studied to determine the class and specificity of lymphocytotoxic antibodies produced during the 6 months following cardiac transplantation. Weekly serum samples were monitored for panel-reactive lymphocytotoxic antibodies (PRA) and donor reactive lymphocytotoxic antibodies using dithiothreitol to determine immunoglobulin class. Sera containing donor-reactive antibodies were further analyzed in a cytotoxic inhibition assay to determine whether the antibodies were directed against HLA or non-HLA determinants. A total of 67 (82%) of the patients produced detectable PRA following transplantation, no correlation was found between PRA and the incidence and severity of rejection. In 33 cases where an HLA specificity was defined, the antibody was not directed against the donor HLA phenotype. In contrast, the 32 (53%) recipients who had formed donor-reactive antibodies within 6 months of operation had required significantly more antirejection therapy (methylprednisolone) than the crossmatch-negative recipients (P less than 0.01). This was the case for both IgG and IgM responses. Of 24 positive donor responses, 18 were found to be specific for HLA antigens. These were both IgM (6 cases) and IgG (12 cases) HLA-specific antibodies, and their occurrence was strongly correlated with rejection (P less than 0.001).