INFLUENCE OF ACUTE REJECTION EPISODES, HLA MATCHING, AND DONOR RECIPIENT PHENOTYPE ON THE DEVELOPMENT OF EARLY TRANSPLANT-ASSOCIATED CORONARY-ARTERY DISEASE/

Background Transplant-associated coronary artery disease (TxCAD) is th e manifestation of chronic rejection in the cardiac allograft. Both im munological and nonimmunological factors contribute to its development . Stratification by the time of development of TxCAD has not been cons idered previously for an extensive transplant series and may provide a means for apportioning relative risk factors appropriately. Specifica lly, TxCAD that develops early may have a pathogenesis different from TxCAD that develops later; ie, immunological factors play a more signi ficant role in early development of TxCAD compared with later forms of the disease or in recipients where it has not been found. Methods and Results Between 1980 and 1994, 550 heart transplant recipients with p ostmortem data or yearly angiograms, donor:recipient serological HLA t yping, and biopsy data were reviewed. Recipients were divided into fou r groups: Very Early (<1 year), Early (1-2 years), Late (3-14 years), and None (clear angio >3 years). There was a significant association b etween the number of histologically proven acute rejeclion episodes wi thin 3 months and at 1 year and the development of early TxCAD. The nu mber of acute rejection episodes within 3 months and 1 year is also si gnificantly related to freedom of development of TxCAD. There was no s ignificant association between the mean number of mismatches for Class I or Class II antigens, nor could any Class I/II phenotype for recipi ent or donor be identified that exerted a protective or deleterious ef fect. A lack of any association or trend with KLA data is demonstrated . Conclusions These differences in pathogenesis between early and late TxCAD help define the importance of acute rejection in the etiology o f chronic cardiac rejection. Stratification by time of development of TxCAD may provide further insight into defining the relative importanc e of other risk factors associated with the development of TxCAD. The lack of association with HLA data is discussed.