The Presence of HLA-Directed Antibodies after Heart Transplantation Is Associated with Poor Allograft Outcome

Tambur, Anat R.; Pamboukian, Salpy V.; Costanzo, María Rosa; Herrera, Nancy D.; Dunlap, Stephanie H.; Montpetit, M.; Heroux, A.

doi:10.1097/01.tp.0000180564.14050.49

Cited by 145 publications

(103 citation statements)

References 20 publications

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“…In multivariable analyses, de novo DSA was found to be an independent predictor for development of BOS1, BOS2 and BOS3, as well as being an independent predictor for poor patient survival. These findings are similar to those seen in both renal 10,16 and cardiac 12,17 transplant studies. In a large study of renal allografts, Lachmann et al showed that DSA detected post-transplant using Luminex single-antigen bead assays were associated with significantly reduced graft survival, 10 whereas we previously found de novo DSA after cardiac transplantation to be an independent predictor of poor patient survival.…”

Section: Discussionsupporting

confidence: 79%

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation

Safavi

Robinson

Soresi

et al. 2014

The Journal of Heart and Lung Transplantation

113

104

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(2014) De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. The Journal of Heart and Lung Transplantation, 33 (12). pp. 1273 -1281 . ISSN 1053 -2498 This version is available from Sussex Research Online: http://sro.sussex.ac.uk/56766/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. There was a significant reduction in patient survival associated with de novo DSA (HR ¼ 1.886, p ¼ 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival. CONCLUSIONS: De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

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Section: Discussionsupporting

confidence: 79%

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation

Safavi

Robinson

Soresi

et al. 2014

The Journal of Heart and Lung Transplantation

113

104

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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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“…Twenty-five of 71 heart transplant recipients developed de novo HLA antibodies in the first year (31). HLA antibodies were associated with cellular rejection (P ϭ 0.0002) and vasculopathy (P Ͻ 0.002), and, most important, class II antibodies were associated with 5-yr survival (P ϭ 0.008).…”

Section: Predictive Value Of De Novo Antibodiesmentioning

confidence: 94%

Antibody Mediated Rejection

Terasaki

Mizutani

2006

Clinical Journal of the American Society of Nephrology

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The Presence of HLA-Directed Antibodies after Heart Transplantation Is Associated with Poor Allograft Outcome

Abstract: Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Cited by 145 publications

References 20 publications

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation

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

Antibody Mediated Rejection

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