Epitope analysis of HLA class I donor specific antibodies in sensitized renal transplant recipients.
OBJECTIVE
The goal of this study was to evaluate the epitope specificity of donor-specific HLA class I antibodies detected in the serum of alloimmunized from a previous renal graft patients.


METHODS
A total of 410 serum samples from 87 patients who had lost a previous graft, were collected every 4 months during a 2-year follow-up period. All recipients and donors were typed for class I HLA-antigens by a standard lymphocytotoxicity technique. To define the specificities of the HLA class I antibodies, two techniques were used in parallel: the antihuman globulin augmented CDC (AHG-CDC) technique and an ELISA technique. The mismatched HLA-antigens and the detected HLA class I antibodies were categorized as intra-cross-reactive group mismatches (intra-CREGs-MMs) and other-CREG-MMs. For each sensitized patient actual and at risk epitope specificities were defined.


RESULTS
Thirty-eight patients (43.7%) had developed IgG HLA class I-specific antibodies with stable specificities against mismatched alloantigens from the previous graft. A total of 60 antibody reactivity patterns and 82 specificities against private and public epitope were recognized. Patients with only intra-CREGs-MMs produced HLA class I-specific antibodies less frequently than patients with only other-CREG-MMs, although the difference was nearly statistically significant (P=0.053). All HLA class I donor-specific antibodies were considered to have specificities against the private epitopes of the mismatched graft HLA-antigens. In the cases where HLA class I alloreactivity was spreading to more than one donor antigens, we considered that the detected antibodies had specificities against the private and the shared between the alloantigens epitope(s). No epitope-specific antibodies were detected against shared epitopes between the mismatched alloantigens and the HLA-antigens of the patients. In 11/38 cases (28.9%) HLA class I alloreactivity spreading to non-graft antigens was detected. These antibodies were directed against HLA-antigens that share epitope(s) and have strong serological reactivity with the immunogenic alloantigens.


CONCLUSIONS
Our data show that a small number of private and public alloepitopes seem to be responsible for antibody production in patients sensitized from a previous graft. A detailed description of these HLA-epitopes, in the context of clinical graft complications, may lead to an improved organ allocation strategy.
Department of Immunology and National Tissue Typing Center, General Hospital Georgios Gennimatas, Greece.
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AC
Papassavas
A
A
Iniotaki-Theodoraki
J
J
Boletis
A
A
Kostakis
C
C
Stavropoulos-Giokas
D000918:Antibody Specificity; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D016030:Kidney Transplantation
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens