title: Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.
abstract: BACKGROUND
  Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies.
  
  
  METHODS
  We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data.
  
  
  RESULTS
  Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013).
  
  
  CONCLUSIONS
  These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.
authors.affiliation: Tissue Typing Laboratory, Addenbrooke's NHS Trust, Cambridge, England.
authors.forename: C J
authors.initials: CJ
authors.lastname: Taylor
authors.forename: S I
authors.initials: SI
authors.lastname: Smith
authors.forename: L D
authors.initials: LD
authors.lastname: Sharples
authors.forename: J
authors.initials: J
authors.lastname: Parameshwar
authors.forename: N R
authors.initials: NR
authors.lastname: Cary
authors.forename: M
authors.initials: M
authors.lastname: Keogan
authors.forename: J
authors.initials: J
authors.lastname: Wallwork
authors.forename: S R
authors.initials: SR
authors.lastname: Large
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D006680:HLA Antigens