The influence of histocompatibility on graft rejection and graft survival within a single center population of heart transplant recipients

Background. We report a consecutive single center series of 261 patients wh o received first orthotopic heart transplants from 1986 to 1997, The 1- and 5-year graft survivals were 78 and 68%, The influence of histocompatibilit y was investigated by comparing graft survival and numbers of treated rejec tion episodes with HLA-A, -B, and -DR mismatches over different time period s. Findings. Recipients with six mismatches for HLA-AS-B+-DR combined (13.4%) had reduced survival at 7 years (47%) when compared with other recipients ( 64%), In the first year of transplant, recipients with four HLA-AS-B mismat ches had significantly reduced actuarial graft survival (P=0,03) with the g reatest influence apparent at 6 months [0-3 mismatches (n=193) 85% versus 4 mismatches (n=68) 69%; P=0,005, OR=2,1], For 182 recipients with functioni ng hearts at 1 year, the number of rejection episodes treated within this t ime was strongly influenced by HLA-DR mismatch [0 DR mismatch (n=15) mean 1 .2 rejection episodes versus 1 DR mismatch (n=76) mean 2.7 rejection episod es versus 2 DR mismatches (n=91) mean 3.8 rejection episodes: P=0,0002], Of these 182 transplants, recipients who had more than four treated rejection episodes during the first year had a significantly reduced 7- year surviva l [< 5 rejection episodes (n=133) 85% versus more than four rejection episo des (n=49) 66%; P=0,02, OR=3,4], as did those with two HLA-DR mismatches [0 +1 mismatch (n=91) 87% versus 2 mismatches (n=91) 70%; P<0,05, OR=2,4], Interpretation. We show that graft loss in the first 6 months of transplant is significantly influenced by four HLA-A+-B mismatches. HLA-DR mismatch s ignificantly increases the number of rejection episodes within the first ye ar, without influencing graft survival. After 12 months both >4 rejection e pisodes in the first year and two HLA-DR mismatches are markers for late gr aft loss. We postulate that immunological graft loss in the first 6 months is dominated by the direct allorecognition pathway driven by HLA-DR mismatc h. This mechanism is later lost or suppressed. Our data highlight HLA-DR mi smatch as a marker for late graft loss and we show an advantage to avoiding transplanting hearts with six HLA-A+-B+-DR mismatches and to minimizing HL A-DR mismatches whenever possible.