title: Serum analysis after transplant nephrectomy reveals restricted antibody specificity patterns against structurally defined HLA class I mismatches.
abstract: This study deals with HLA-mismatched kidney transplants that have been removed following rejection. Sera from 27 patients were screened for HLA-specific antibodies by direct complement-dependent lymphocytotoxicity with HLA-typed cell panels. Circulating donor-specific antibodies were detected in 3 cases (11%) before and in 26 cases (97%) after allograft nephrectomy. These findings demonstrate the production of donor-specific antibodies in patients with rejected transplants, but in most cases, they were undetectable before nephrectomy, because the graft had adsorbed them. With an HLAMatchmaker-based serum analysis program, we observed restricted antibody specificity patterns against amino acid triplet-defined epitopes on donor HLA-A,B antigens. Many donor triplets were non-reactive while others were apparently recognized by antibodies. In some patients, the donor triplet specific antibodies persisted for a long time whereas in many other patients, they became undetectable after a few months. The characterization of the antibody specificity profiles of post-allograft nephrectomy sera is clinically useful in defining criteria of HLA mismatch acceptability for sensitized patients awaiting another transplant. It provides also opportunities for determining the relative immunogenicity of mismatched triplets.
authors.affiliation: Division of Transplantation Pathology and CLSI Tissue Typing Laboratory, Department of Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, 15261 USA.
authors.forename: Oyedele A
authors.initials: OA
authors.lastname: Adeyi
authors.forename: Alin L
authors.initials: AL
authors.lastname: Girnita
authors.forename: Judy
authors.initials: J
authors.lastname: Howe
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marrari
authors.forename: Yehia
authors.initials: Y
authors.lastname: Awadalla
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.forename: Joan
authors.initials: J
authors.lastname: Martell
authors.forename: Adrian
authors.initials: A
authors.lastname: Zeevi
authors.forename: Ron
authors.initials: R
authors.lastname: Shapiro
authors.forename: Michael
authors.initials: M
authors.lastname: Nalesnik
authors.forename: Parmjeet
authors.initials: P
authors.lastname: Randhawa
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: René J
authors.initials: RJ
authors.lastname: Duquesnoy
mesh_terms: D000328:Adult; D000465:Algorithms; D001787:Blood Group Incompatibility; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009392:Nephrectomy
chemical_list: D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies