Clinical Relevance of Anti-HLA Antibodies Detected by Flow-Cytometry Bead-Based Assays—Single-Center Experience

Mihaylova, А.; Baltadjieva, Daniela; Boneva, Petia; Ivanova, Milena; Penkova, Kalina; Marinova, Daniela; Mihailova, Snezhina; Paskalev, Emil; Simeonov, Petar; Naumova, Elissaveta

doi:10.1016/j.humimm.2006.07.011

Cited by 39 publications

(31 citation statements)

References 40 publications

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“…These data indicate also an association between the number of mismatched eplets and the detection of antibodies reacting with donor antigens. They are similar to the reported correlations between HLA antibody responses and the number of structurally defined mismatched epitopes (triplets or amino acid residues) on transplant donor antigens [39][40][41]. However, antibody absorption by the allograft may also explain the low detection rate of donorspecific anti-DR antibodies.…”

Section: Eplet Differences and Antibodies To Drb1 Drb3 Drb4 And Drbsupporting

confidence: 87%

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: Eplet Differences and Antibodies To Drb1 Drb3 Drb4 And Drbsupporting

confidence: 87%

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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“…Rejection and DGF rates were found higher in the posttransplant PRA positive group. In our study, the rate of DGF in the PRA positive patient group was also higher than the PRA negative group which is in conformity with the study by Mihaylova et al (1). Anti-HLA antibodies in the early period after renal transplantation may harm the graft endothelium and cause DGF (14).…”

Section: Discussionsupporting

confidence: 92%

“…The role of sensitive solid-phase assays in the detection of anti-HLA antibodies has been growing recently (1). Here, we investigate the incidence of HLA-directed antibodies developed after renal transplantation and their impact on graft rejection and outcome in kidney recipients using sensitive and specific flow-cytometry bead-based techniques.…”

Section: Discussionmentioning

confidence: 99%

“…Despite reliable pre-transplant screening methods and improvement of immunosuppression therapy, failures of kidney allografts are still occurred because of cellular and/or humoral mediated rejections (1). Several recent studies evaluated the prevalence of human leukocyte antigen (HLA)-specific antibodies and the clinical importance of these antibodies in acute allograft rejection (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…HLA antibodies developed in the early term of transplantation damages allograft more than antibodies developed after 1 year of transplantation (11). Post-transplantation alloantibody development in the early period may be associated with reperfusion and prolonged cold ischemia time [a chief factor leading to delayed graft function (DGF)] induced activation of endothelium and impaired cytokine gene expression, release of proinflammatory cytokines, and upregulation of HLA and adhesion molecules (1,12,13). These events lead to stimulation of the immune response in the early post-transplantation period and, as a consequence, to HLA antibody production.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Long-Term Effects of Antibodies against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year after Renal Transplantation

Ayna¹,

Çalışkan²,

Çiftçi³

et al. 2013

Balkan Med J

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Objective: In this study, we aimed to investigate the incidence, dynamics and profiles of human leukocyte antigen (HLA)-directed antibodies developed after transplantation and their impact on graft rejection and outcome in kidney recipients.Study Design: Prospective follow-up study.Material and Methods: A total of 56 kidney recipients were monitored at 1 st , 6 th and 12 th months for the development of anti-HLA antibodies using bead based flow-cytometry assays (Flow PRA tests).Results: In 21 (37.5%) patients, panel reactive antibodies (PRA) was positive after transplantation, however, in 35 (62.5%) patients PRA was found negative. Twelve (57.1%) patients with post-transplantation HLA-reactive antibodies [PRA (+)] and 8 (22.9%) patients with no detectable alloantibodies [PRA (-)] were developed allograft rejection (p=0.010). In the PRA positive patient group the rates of early period infection and delayed graft function (DGF) were higher than the PRA negative patient group. Serum creatinine levels of PRA positive group at 6. and 12. months after transplantation were significantly higher than the PRA negative group (p=0.015 and p=0.048, respectively). The rejection rates of patients who had class I and II HLA antibodies were significantly higher than the patients who had either class I or II HLA antibodies (p=0.011). Acute rejection rates were significantly higher in patients who had class I and II HLA antibodies at the first month (p=0.007). Conclusion:Higher occurrence of rejection episodes in PRA positive group may show the importance of anti-HLA antibody monitoring using Flow-PRA after renal transplantation as a prognostic marker in terms of graft survival.

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HLAMatchmaker-Defined Triplet Matching Is Not Associated with Better Survival Rates of Patients with Class I HLA Allele Mismatched Hematopoietic Cell Transplants from Unrelated Donors

Duquesnoy¹,

Spellman²,

Haagenson³

et al. 2008

Biology of Blood and Marrow Transplantation

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This report addresses the concept that permissible HLA mismatching, i.e. mismatches that do not generate an allogeneic response, in hematopoietic stem cell transplantation (HCT) can be determined with structural similarity of polymorphic regions. We have applied the triplet version of a structural algorithm called HLAMatchmaker that considers short sequences involving polymorphic amino acid residues on the molecular surface as key elements of immunogenic epitopes. The triplet matching effect was analyzed in a National Marrow Donor Program dataset consisting of 744 unrelated hematopoietic cell transplantation cases with one HLA-A,-B or -C mismatch and 1690 fully HLA-A,-B,-C,-DR,-DQ allele matched cases. In multivariate models adjusting for other significant clinical risk factors, the degree of triplet mismatching did not significantly correlate with patient survival, engraftment or acute graft versus host disease. Other structurally based strategies should be pursued to identify permissible HLA mismatches in HCT.

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Clinical Relevance of Anti-HLA Antibodies Detected by Flow-Cytometry Bead-Based Assays—Single-Center Experience

Cited by 39 publications

References 40 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

Long-Term Effects of Antibodies against Human Leukocyte Antigens Detected by Flow Cytometry in the First Year after Renal Transplantation

HLAMatchmaker-Defined Triplet Matching Is Not Associated with Better Survival Rates of Patients with Class I HLA Allele Mismatched Hematopoietic Cell Transplants from Unrelated Donors

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