Detection of Hla Class I- And Class Ii-Specific Antibodies by Flow Cytometry and Pra-Stat Screening in Renal Transplant Recipients

Harmer, A.; Heads, A; Vaughn, R W

doi:10.1097/00007890-199706270-00021

Cited by 42 publications

(19 citation statements)

References 8 publications

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“…Preformed anti-donor class II antibodies increase the risk of transplant failure [1][2][3][4][5][6][7][8][9] and the post-transplant development of anti-class II antibodies is associated with a higher incidence of acute and chronic rejection [10][11][12][13][14][15][16][17][18][19] Current class II matching strategies for kidney transplantation consider only the HLA-DR antigens controlled by the DRB1 locus but mismatching for HLA-DQ and HLA-DP may also lead to lower graft survival rates [20][21][22][23][24][25]. Newer serum screening methods such as ELISA, Flow Cytometry and Luminex have greatly enhanced the detection of anti-HLA-DQ and HLA-DP antibodies and their association with transplant rejection [2,7,[26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Duquesnoy

Awadalla

Lomago

et al. 2008

Transplant Immunology

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This report describes a detailed analysis how donor-specific HLA class II epitope mismatching affects antibody reactivity patterns in 75 solid organ transplant recipients with an in situ allograft and who were considered for retransplantation. Sera were tested for antibodies in a sensitive antigenbinding assay (Luminex) with single class II alleles. Their reactivity was analyzed with HLAMatchmaker, a structural matching algorithm that considers so-called eplets to define epitopes recognized by antibodies. Only 24% of the patients showed donor-specific anti-DRB1 antibodies and there was a significant correlation with a low number of mismatched DRB1 eplets. This low detection rate of anti-DRB1 antibodies may also be due to allograft absorption. In contrast, antibodies to DRB3/4/5 mismatches were more common. Especially, 83% of the DRB4 (DR53) mismatches resulted in detectable antibodies against an eplet uniquely found on DR53 antigens. Donor-specific DQB mismatches led to detectable anti-DQB antibodies with a frequency of 87%. Their specificity correlated with eplets uniquely found on DQ1-4. The incidence of antibodies induced by 2-digit DQA mismatches was 64% and several eplets appeared to play a dominant role. These findings suggest that both α and β chains of HLA-DQ heterodimers have immunogenic epitopes that can elicit specific antibodies. About one-third of the sera had anti-DP antibodies; they reacted primarily with two DPB eplets and an allelic pair of DPA eplets.These data demonstrate that HLA class II reactive sera display distinct specificity patterns associated with structurally defined epitopes on different HLA-D alleles.

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Section: Introductionmentioning

confidence: 99%

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Duquesnoy

Awadalla

Lomago

et al. 2008

Transplant Immunology

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“…However, our absorption experiments demonstrated that this assay was capable to detect antibodies directed against specific HLA-DR antigens and was not interfered by other molecules. Recently, antigen-specific immunotests using purified antigens coated in microtiter plate [30] or beads [31,32] were developed for the characterization of HLA class II antibodies in ELISA or flow cytometry technique, respectively. However, some epitopes could be destroyed by the isolation processes which might impair the binding of human alloantibodies.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA-DR Antibodies and Graft Rejection in Renal Transplantation: Posttransplant Analysis Using the Monoclonal Antibody-Specific Immobilization of Leukocyte Antigens Assay (MAILA)

Renner¹,

Santoso²,

Müller‐Steinhardt³

et al. 2004

Transfus Med Hemother

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Background: The clinical impact of HLA-DR alloantibodies in renal transplantation is still controversial. This may be partly due to the lack of specificity and sensitivity of current detection methods, e.g. complement-dependent cytotoxicity test employing B lymphocytes as target antigens. Patients and Methods: In this study, we analyzed the incidence and specificity of HLA-DR antibodies after renal transplantation by use of the antigen-specific capture assay MAILA. 53 primary cadaver kidney recipients were recruited for a prospective study and were retrospectively assigned to the following groups: 20 patients with unsuspicious clinical course within the first 3 months after transplantation (control group), 20 patients undergoing histologically proven acute rejection within the first 3 months after transplantation, and 13 patients with chronic rejection 1 year or later after transplantation. 105 patients’ sera collected prospectively were analyzed by MAILA using 13 homozygous B-lymphoblastoid cell lines (B-LCL) carrying the common HLA-DR specificities. Results: In the control group, only 1 of 19 patients (5.3%) without acute rejection revealed HLA-DR antibodies after transplantation. In contrast, HLA-DR alloantibodies could be detected post transplant in 36.8% (7/19) and 69.2% (9/13) of patients with acute and chronic rejection, respectively. The frequency of HLA-DR antibodies present in both study groups was significantly higher in comparison to the control group. Of the 17 patients who received a graft across a donor recipient HLA-DR mismatch, 5 patients exhibited donor-specific alloantibodies. However, the majority of antibodies detected was not specific for mismatched HLA-DR alloantigens. Conclusion: HLA-DR antibodies were significantly associated with transplant rejection in first cadaver renal transplantation, especially in patients undergoing chronic rejection. Although donor specificity was not observed in the majority of patients, monitoring of HLA-DR antibodies might support diagnosis of graft rejection.

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“…Newer assays, utilizing more sensitive methods, e.g. enzyme-linked immunosorbent assay (ELISA) and Flow Bead, and using specific HLA antigens as targets have been introduced to identify antibodies specific to HLA antigens (1094)(1095)(1096)(1097)(1098)(1099). Knowing whether there are antibodies specific to HLA antigens helps in correctly interpreting the crossmatch results.…”

Section: The Evaluation Of Renal Transplant Candidates: Clinical Pracmentioning

confidence: 99%

“…Recently, newer assays have been introduced that use more sensitive methods (ELISA and Flow Bead), and use specific soluble HLA target antigens immobilized in tray wells or on microbeads, to identify sera with IgG antibodies to HLA antigens (1094)(1095)(1096)(1097)(1098)(1099). Results from the ELISA-PRA have been shown to be more predictive of a posttransplant acute rejection and graft loss than the membrane dependent AHG-PRA assay (1094)(1095)(1096)(1097)(1098).…”

Section: The Evaluation Of Renal Transplant Candidates: Clinical Pracmentioning

confidence: 99%

“…Results from the ELISA-PRA have been shown to be more predictive of a posttransplant acute rejection and graft loss than the membrane dependent AHG-PRA assay (1094)(1095)(1096)(1097)(1098). The Flow Bead PRA (Flow PRA) procedure can detect IgG antibody to HLA antigens in sera that are reported to be non-reactive (0% PRA) by ELISA (1093).…”

Section: The Evaluation Of Renal Transplant Candidates: Clinical Pracmentioning

confidence: 99%

See 1 more Smart Citation

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

2001

American Journal of Transplantation

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Detection of Hla Class I- And Class Ii-Specific Antibodies by Flow Cytometry and Pra-Stat Screening in Renal Transplant Recipients

Abstract: These results suggest that PRA-STAT is a useful technique for the detection of both HLA class I- and class II-specific antibodies, rather than only class I-specific antibodies as previously described.

Cited by 42 publications

References 8 publications

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes

Association of HLA-DR Antibodies and Graft Rejection in Renal Transplantation: Posttransplant Analysis Using the Monoclonal Antibody-Specific Immobilization of Leukocyte Antigens Assay (MAILA)

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

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