Determination of Hla-A,b Residue Mismatch Acceptability for Kidneys Transplanted Into Highly Sensitized Patients

BACKGROUND: During the 12th International Histocompatibility Workshop, a collaborative study between 35 laboratories was conducted on a group of highly allosensitized patients who had received a kidney transplant from 1981 to 1995. The major goal of the study was to assess how serum screening against a large cell panel could determine donor HLA mismatch acceptability in relation to graft outcome. METHODS: Twenty laboratories participated in an extensive screening of 92 high panel-reactive antibody (PRA) sera from patients at 29 transplant centers worldwide; each patient had received a kidney allograft from an HLA-A,B mismatched unrelated donor. Screening was done by complement-dependent lymphocytotoxicity and antihuman globulin augmentation techniques using a common protocol and shared standardized reagents. After an extensive quality-control assessment, we selected data from 14 participants who had screened the sera against a combined panel of 535 HLA-typed cells. RESULTS: With the 2x2 table-based Multiscreen computer program, we could readily determine for virtually every patient the significant correlations between serum reactivity and the presence of panel cell markers, including private and public HLA-A,B epitopes and amino acid residues assigned from published sequencing data. Donor mismatch acceptability was assessed at the amino acid residue level. In the complement-dependent lymphocytotoxicity (n=49; PRA=84.1+/-12.1%) and antihuman globulin (n=60; PRA=92.5+/-5.8%) groups, the 3-month graft survivals were 28% and 30% lower for unacceptable residue mismatches. CONCLUSIONS: These studies underscore the importance of a comprehensive serum screening analysis in the selection of appropriately mismatched donors for highly sensitized transplant patients.