The Predictive Value of Epitope Analysis in Highly Sensitized Patients Awaiting Renal Transplantation

Laundy, G. J.; Bradley, Benjamin A.

doi:10.1097/00007890-199504000-00022

Cited by 10 publications

(15 citation statements)

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“…Our observations are in agreement with those of other studies, which suggest that the immunogenic HLA class I specific epitope targets associated with the sera of highly sensitized patients can be predicted from the results of routine screening for the detection of HLA specific antibodies (Laundy & Bradley, 1995). Knowledge of the actual HLA class I specific epitope targets would permit prediction of acceptable mismatches and identification of suitable donors for highly sensitized patients (Duquesnoy et al ., 1991; Laundy & Bradley, 1994; Laundy & Bradley, 1995; Papassavas et al ., 2000a,b). Thus, in samples with high PRA levels, sensitive screening assays such as AHG‐CDC, flow cytometry and an ELISA technique should be used in parallel for the detection of HLA class I specific antibodies.…”

Section: Discussionsupporting

confidence: 93%

“…The shared or public epitopes have been used to define the major serological cross‐reactive group (CREG) epitope clusters (Fuller et al ., 1990a,b). High panel reactive antibodies (PRA) sera have been assumed to be multispecific, but it has become apparent that these sera generally contain a limited number of antibodies directed against very common, highly immunogenic epitopes that are expressed mainly on class I HLA antigens (Laundy & Bradley, 1995; Papassavas et al ., 2000a).…”

Section: Introductionmentioning

confidence: 99%

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Definition of permissible and immunogenic HLA antigens based on epitope analysis of the HLA specific antibodies produced in sensitized patients

Papassavas

Stavropoulos-Giokas

Boletis

et al. 2002

European Journal of Immunogenetics

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The goal of this study was to develop an accurate protocol whereby detection of acceptable HLA-A and -B mismatches is based on epitope analysis of HLA class I specific antibodies detected in the serum of highly sensitized patients awaiting a kidney retransplant. A total of 400 serum samples from 44 highly sensitized patients with panel reactive antibodies (PRA) of > or = 60% were collected during a 3-year follow-up period. All patients had been sensitized from a previous graft. In order to define the specificities of the HLA class I specific antibodies, two techniques were used in parallel: the antihuman globulin augmented complement-dependent cytotoxicity (CDC) technique and an enzyme-linked immunoabsorbent assay (ELISA) technique. Epitope identification was based on class I HLA antigen sequencing, where the unique epitope configuration on one HLA antigen represented the private epitope of the specific HLA antigen, and epitopes shared by more than one HLA antigen represented public determinants. The epitope prediction for the immunogenic HLA epitopes was based on an MHC database. For each highly sensitized patient, antibody specificities against actual and 'at risk' epitopes were defined. Following epitope analysis, all HLA antigens that did not express the actual and/or 'at risk' immunogenic epitopes were considered as acceptable mismatches of epitope analysis. The cytotoxicity of highly sensitized patients was determined using two different panels of selected, separated T lymphocytes. HLA class I specific IgG antibodies against 69 actual and 86 'at risk' epitopes were detected. In all patients, a large number of acceptable mismatches were defined. These included a large number of HLA antigens, corresponding to both HLA-A and -B loci. Our study introduces an accurate protocol for the detection of acceptable mismatches in highly sensitized patients. According to this protocol, the detailed description of immunogenic HLA specific epitope targets, against which HLA class I specific antibodies are directed, is a useful tool for the detection of acceptable mismatches in highly sensitized patients. This may lead to reduced production of HLA class I specific antibodies and, consequently, improved graft survival.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Definition of permissible and immunogenic HLA antigens based on epitope analysis of the HLA specific antibodies produced in sensitized patients

Papassavas

Stavropoulos-Giokas

Boletis

et al. 2002

European Journal of Immunogenetics

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“…Patient sera with low levels of panel reactivity mostly have antibodies specific for a single antigenic epitope present on individual HLA specificities (private epitopes) (17). In contrast, sera with high PRA predominantly contain antibody populations with specificity for antigenic epitopes that are common to several HLA specificities (public epitopes), termed cross‐reactive groups (CREGs) (18–21). In humans, all HLA‐A and B antigens can be defined in just 10 major CREGs that are considered to constitute the main B‐cell target epitopes (22).…”

Section: Discussionmentioning

confidence: 99%

Sensitisation to Swine Leukocyte Antigens in Patients with Broadly Reactive HLA Specific Antibodies

Oostingh¹,

Davies²,

Tang³

et al. 2002

American Journal of Transplantation

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“…Immunologic status of potential kidney transplant recipients has an impact on transplant outcome. The presence of HLA antibodies is associated with reduced graft survival (1–4). Therefore, accurate detection of these antibodies is important for identifying the sensitized patients, who are at the high risk of post‐transplant rejection.…”

mentioning

confidence: 99%

CD30, a marker to detect the high‐risk kidney transplant recipients

Spiridon¹,

Nikaein²,

Lerman

et al. 2008

Clinical Transplantation

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The Predictive Value of Epitope Analysis in Highly Sensitized Patients Awaiting Renal Transplantation

Cited by 10 publications

References 0 publications

Definition of permissible and immunogenic HLA antigens based on epitope analysis of the HLA specific antibodies produced in sensitized patients

Definition of permissible and immunogenic HLA antigens based on epitope analysis of the HLA specific antibodies produced in sensitized patients

Sensitisation to Swine Leukocyte Antigens in Patients with Broadly Reactive HLA Specific Antibodies

CD30, a marker to detect the high‐risk kidney transplant recipients

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