Effect of HLA mismatching and antibody status on “homovital” aortic valve homograft performance

Background. Recipients of “homovital” aortic valve homografts are known to produce specific antibodies to human leukocyte antigen (HLA) determinants present on the cellular compartment of the valve tissue; however, the clinical significance of these antibodies is unknown. Data from 182 patients receiving homovital aortic valve homografts has been analyzed to determine the impact of HLA disparity and HLA antibody production on survival and function of the homograft. Methods. Human leukocyte antigen mismatch data were available for 127 patients (mean follow-up, 6.02 ± 0.26 years). Two patients were considered well matched for HLA A+B antigens (zero or one mismatch) compared with 125 poorly matched (two to four mismatches). Nine patients had a zero HLA-DR mismatch compared with 52 with one mismatch and 59 patients completely mismatched for DR antigens. Results. There was no significant association between the degree of HLA mismatch for either class I or class II antigens whether the loci were considered alone or in combination (ie, A, B, DR, AB, or ABDR mismatching) with markers of long-term valve function including patient mortality, reoperation, valve degeneration, valve stenosis, presence of regurgitation, and postoperative New York Heart Association class. One hundred thirty-six of 167 (82%) were found to have produced antibodies after operation (mean time after operation, 6.42 ± 0.58 years). In 61 cases both antibody specificity and donor HLA typing was available. In 92% of these, the antibodies were of the IgG subclass and were specific for the HLA class I molecules of the donor. The presence of HLA antibodies was associated with an increase in the frequency of mild valve stenosis (not significant) compared with those patients who did not develop HLA antibodies (antibody negative = 9.7%; panel reactive antibodies <50% = 29.1%; and panel reactive antibodies >50% = 22.2%; not significant). There was also an increased prevalence of valve degeneration associated with HLA antibodies. The actuarial freedom from valve degeneration for the 35 HLA antibody-negative patients was 100% at 1, 5, and 10 years compared with 100% at 1 year, 97% at 5 years, and 92% at 10 years for 55 patients with panel reactivity less than 50%, and 98% at 1 year, 94% at 5 years, and 88% at 10 years for the 77 patients who were highly sensitized (not significant). There was no correlation with other markers of long-term valve function. Conclusions. The influence of the immune response on valve function requires further studies involving large numbers of patients followed for a longer period of time. We believe prospective matching for HLA antigens is warranted to produce a well-matched cohort of patients for analysis and to reduce antibody sensitization, which would help to clarify this issue.