Influence of HLA matching and associated factors on aortic valve homograft function

Evidence suggests that the implanted aortic valve homograft suffers eventual loss of function due to early donor-specific antibody and T cell-mediated responses to human leukocyte antigens (HLA). The association between rejection/dysfunction and donor/recipient HLA mismatch for vascularized organ homografts has not been revealed for aortic valve homografts. An aortic valve homograft recipient cohort was studied to determine whether HLA mismatch and associated factors predicted homograft dysfunction.

Both donor and recipient HLA type was obtained for 162 recipients of cryopreserved aortic valve homografts between 1986 and 1998. Structural deterioration of the homograft was defined by echocardiography as at least moderate aortic stenosis or regurgitation. Patients' records were searched for postoperative fever, ABO blood type disparity, and other associated factors. HLA class 1 (A and B antigens) were typed serologically, and HLA class 2 (DR antigens) by molecular genotyping. Associations were analyzed using chi-square tests and Kaplan-Meier curves of freedom from structural deterioration in all patients, and in those with > or =5 years of follow up. Cox regression was used to determine independent predictors of structural deterioration.

Class 2 antigen mismatch had a significant association (p = 0.04) with decrease in cryopreserved aortic valve homograft freedom from structural deterioration in patients with long-term follow up (> or =5 years). In addition, there was an important difference in frequency of postoperative fever in recipients with two DR mismatches (31.2%), and in those with no or one DR mismatch (16.9%; p = 0.051). Significant associations were not found between homograft dysfunction and HLA mismatch at the class-1 loci. Young age at operation and short time (<4 h) between homograft procurement and cryopreservation were associated with an increase in structural deterioration.

The association between aortic valve homograft dysfunction and HLA DR mismatch suggests that elements of the anti-donor immune response penetrate and damage the homograft. A similar link to postoperative fever indicates that immune stimulation may be an early event. Further investigation will reveal the exact pathways by which this occurs and by which therapy (immunosuppression of the recipient, genetic engineering of the donor graft, or other techniques) this recipient anti-donor response can be modified.