BACKGROUND AND AIM OF THE STUDY: As the cause of allograft heart valve degeneration is poorly understood, the study aim was to investigate the host antibody response to allograft valve implantation. METHODS: Sera were obtained from 92 recipients of allograft heart valves (61 pulmonary, 31 aortic). Sera were tested for anti-HLA class I antibodies by ELISA and complement-dependent cytotoxicity (CDC) methods, and anti-HLA class II antibodies by ELISA. Specificities of recipient anti-HLA class I antibodies were defined by standard CDC testing against a panel of T lymphocytes from 80 blood donors. Donor valve HLA typing was performed on stored donor DNA samples using molecular methods. The presence of donor-specific anti-HLA class I antibodies was hence defined in recipient sera. The presence of anti-HLA antibodies and donor-specific anti-HLA class I antibodies were correlated with function of allograft valves at the most recent echocardiographic follow up. RESULTS: At a mean of 3.0 years (range: 0.3-5.4 years) after allograft implantation, 96% (87/92) and 82% (75/92) of patients were positive for anti-HLA class I and II antibodies, respectively, by ELISA testing. Some 68% (61/90) of patients were positive for anti-HLA class I antibody (PRA > 5%) by CDC testing. PRA levels decreased with greater postoperative interval (r = -0.31, p = 0.003). In 68 recipients where donor HLA type was defined, 54% (37/68) of patients had antibodies specific to at least one donor HLA class I antigen. In 87 patients with a recent echocardiographic examination available for analysis (at a mean of 3.5 +/- 1.6 years postoperatively), there was no association between valve dysfunction and antibody status. CONCLUSION: Anti-HLA class I and II antibodies were detected by ELISA methods in most patients after allograft implantation extending to 5.4 years. The clinical significance of these findings is unclear, as no correlation was found between the prevalence of anti-HLA antibody and echocardiographic parameters of valve dysfunction at a mean of 3.5 years follow up.
BACKGROUND AND AIM OF THE STUDY: As the cause of allograft heart valve degeneration is poorly understood, the study aim was to investigate the host antibody response to allograft valve implantation. METHODS: Sera were obtained from 92 recipients of allograft heart valves (61 pulmonary, 31 aortic). Sera were tested for anti-HLA class I antibodies by ELISA and complement-dependent cytotoxicity (CDC) methods, and anti-HLA class II antibodies by ELISA. Specificities of recipient anti-HLA class I antibodies were defined by standard CDC testing against a panel of T lymphocytes from 80 blood donors. Donor valve HLA typing was performed on stored donor DNA samples using molecular methods. The presence of donor-specific anti-HLA class I antibodies was hence defined in recipient sera. The presence of anti-HLA antibodies and donor-specific anti-HLA class I antibodies were correlated with function of allograft valves at the most recent echocardiographic follow up. RESULTS: At a mean of 3.0 years (range: 0.3-5.4 years) after allograft implantation, 96% (87/92) and 82% (75/92) of patients were positive for anti-HLA class I and II antibodies, respectively, by ELISA testing. Some 68% (61/90) of patients were positive for anti-HLA class I antibody (PRA > 5%) by CDC testing. PRA levels decreased with greater postoperative interval (r = -0.31, p = 0.003). In 68 recipients where donor HLA type was defined, 54% (37/68) of patients had antibodies specific to at least one donorHLA class I antigen. In 87 patients with a recent echocardiographic examination available for analysis (at a mean of 3.5 +/- 1.6 years postoperatively), there was no association between valve dysfunction and antibody status. CONCLUSION: Anti-HLA class I and II antibodies were detected by ELISA methods in most patients after allograft implantation extending to 5.4 years. The clinical significance of these findings is unclear, as no correlation was found between the prevalence of anti-HLA antibody and echocardiographic parameters of valve dysfunction at a mean of 3.5 years follow up.