Public epitope specificity of HLA class I antibodies induced by a failed kidney transplant: alloantibody characterization by flow cytometric techniques.
Transplantation
; 81(9): 1298-305, 2006 May 15.
Article
em En
| MEDLINE
| ID: mdl-16699458
ABSTRACT
BACKGROUND:
Patients whose kidney grafts fail develop alloantibodies that react with many HLA molecules. We analyzed the epitope specificity of HLA class I alloantibodies in the sera of 55 patients who had been sensitized by kidney grafts, and investigated the immunogenicity of various polymorphic epitopes.METHODS:
HLA class I alloantibodies were detected and characterized by flow cytometry (FlowPRA beads). Potential "immunizing epitopes" were identified by comparing the amino acid sequences of HLA class I antigens/alleles of the donor, recipient and the antibody-reactivity pattern.RESULTS:
In the 55 anti-HLA class I-positive patients, 82 different antibody reactivity patterns were identified; all but 5 (94%) were determined by a "public epitope" of donor HLA-A and/or -B molecules. Forty-five of 50 patients who showed HLA-A Res-MMs with their donors produced HLA-A antibodies, but only 31 of 51 subjects with HLA-B Res-MMs produced HLA-B antibodies (P=0.001; O.R.=5.81). The antibody patterns were specific for a "single" epitope of the mismatched donor molecules in 91% of patients. Forty-three of the 120 (36%) mismatched HLA-A and/or -B epitopes were positively correlated with antibody production. The polymorphic determinants of higher immunogenic capacity were b80N (Bw6-associated) and ab82-83LR (Bw4-associated) public epitopes.CONCLUSIONS:
The humoral immune response against a kidney graft mainly produces HLA class I antibodies specific for "public epitopes" of mismatched donor molecules. A "single" donor-epitope may determine the production of a spread antibody pattern. In renal transplantation, epitope matching is better than HLA antigen matching for avoiding or minimizing development of HLA antibodies.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Classe I
/
Transplante de Rim
/
Isoanticorpos
/
Epitopos
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article