Humoral immune response to human aortic valve homografts

Abstract

The humoral response to homograft valves in humans is largely unknown. The anti-human lymphocyte antigen (HLA) antibody production, specificity, and immunoglobulin class were examined sequentially in 73 patients undergoing aortic valve replacement. In addition, the long-term production of antibodies was examined in a cross-sectional study of 160 patients at periods varying from 1 to 15 years postoperatively. Human lymphocyte antigen antibodies were produced in 17 of 30 antibiotic-sterilized homografts (56%) and in 15 of 15 "homovital" homograft recipients, compared with 6 of the 28 control xenograft recipients (21%) (p < 0.001). The HLA antibodies were immunoglobulin G in all 15 homovital homografts, in 11 of 17 antibiotic-sterilized homografts, and in four of the six xenograft cases. Human lymphocyte antigen specificities could be assigned to the antibodies in 21 cases. In 10 of 11 cases in which donor HLA typing data were available, the antibodies detected were directed against donor HLA class I antigens. Of six possible determinants of HLA antibody production, the type of homograft valve implanted (homovital or antibiotic sterilized) correlated with antibody formation. In the cross-sectional study, 66 of the 85 homovital homograft recipients tested for HLA antibodies after 1 year were found to have antibodies, compared with 29 of 75 antibiotic-sterilized homograft recipients (p = 0.00003). We conclude that homografts appear to stimulate a strong donor HLA-specific antibody response, particularly of the immunoglobulin G class. This is most common in homovital valve recipients. These antibodies can persist for 15 years after operation. The clinical significance of this response requires further investigation.