Anti-Human Leukocyte Antigen and Donor-Specific Antibodies Detected by Luminex Posttransplant Serve as Biomarkers for Chronic Rejection of Renal Allografts

Lachmann, Nils; Terasaki, Paul I.; Budde, Klemens; Liefeldt, Lutz; Kahl, Andreas; Reinke, Petra; Pratschke, Johann; Rudolph, Birgit; Schmidt, Danilo; Salama, Abdulgabar; Schönemann, Constanze

doi:10.1097/tp.0b013e3181a44206

Cited by 325 publications

(262 citation statements)

References 33 publications

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“…Recently published studies on pretransplant DSAs focused mainly on deceased donor transplants, as these are most prevalent in, for example, France, Germany, and the United States 17, 18, 19. Studies on living donor transplant are scarce; in a single‐center study, where 324 living donor transplants were analyzed, no significant difference in the 5‐year graft survival of patients with DSAs was found compared with patients with anti–blood type antibody, anti–HLA‐Abs, or no DSAs 20.…”

Section: Discussionmentioning

confidence: 99%

“…For posttransplant DSAs determined using SAB assays, it was already shown that it has an adverse effect on graft survival 18. For our cohort, we can assess only the potential for confounding by de novo DSAs via the average number of HLA mismatches.…”

Section: Discussionmentioning

confidence: 99%

“…While recent large‐cohort studies of the impact of DSAs on graft survival have mainly focused on deceased donor transplants,17, 18, 19 the effect of SAB assay–detected DSAs on living donor transplants has not been studied in large cohorts. In a Japanese single‐center study, 324 living donor kidney transplant recipients were analyzed to investigate the outcome of the 92 kidney transplant recipients with DSAs in combination with anti–blood type, anti–HLA antibodies, or both; all were desensitized before transplant 20.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Kamburova

Wisse

Joosten

et al. 2018

American Journal of Transplantation

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The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Kamburova

Wisse

Joosten

et al. 2018

American Journal of Transplantation

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“…In both renal and cardiac transplantation there is evidence that development of HLA-specific antibodies, particularly if donorspecific, are associated with poor graft survival. [10][11][12] The development of BOS is the major cause of death beyond the first year after lung transplantation. 1,13 BOS is defined according to loss of lung function (forced expiratory volume in 1 second [FEV 1 ]) in proportion to maximal baseline value obtained post-transplantation in the absence of known acute causes of declining FEV 1 , such as acute rejection and infection.…”

mentioning

confidence: 99%

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

115

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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“…While DSA, either alone or in combination with microscopic evidence of microcirculation injury with or without C4d staining on kidney biopsy, are of most concern, the development of de novo nondonor HLA-specific (third party) antibodies are also, for reasons that are not clear, sometimes associated with an increased risk of graft loss (2,(4)(5)(6). One possible explanation for the association between de novo third party HLA-specific antibodies and inferior transplant outcome is that third party antibodies occur in conjunction with low level DSA or other non-HLAspecific antibodies that are not detected in the circulation because they have been absorbed by the kidney graft (2).…”

Section: Introductionmentioning

confidence: 99%

Transfer of HLA-Specific Allosensitization From a Highly Sensitized Deceased Organ Donor to the Recipients of Each Kidney

Maxfield

Taylor

Kosmoliaptsis

et al. 2015

American Journal of Transplantation

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We report for the first time the adoptive transfer of donor HLA‐specific allosensitization in two recipients following kidney transplantation from a highly sensitized donor. Kidneys from a donation after circulatory death donor were transplanted into two nontransfused, HLA‐specific antibody negative males receiving their first transplant. Antibody screening 7 days after transplant showed high level de novo IgG HLA class I‐ and class II‐specific antibodies in both recipients, with largely overlapping antibody profiles but no antibodies to donor HLA. The unusually rapid appearance of de novo alloantibodies in immunosuppressed nonsensitized recipients and absence of donor HLA‐specific antibody prompted testing of stored donor serum that revealed high antibody levels with specificities very similar to those seen in both recipients, but in addition the presence of strong antibodies to each recipient HLA. Alloantibody levels gradually declined but were still detectable at 3 months. These findings suggest that alloreactive passenger B cells/plasma cells within the kidneys of highly sensitized donors may give rise to rapid development of posttransplant de novo HLA‐specific alloantibodies. While the clinical significance of this phenomenon is uncertain it provides one explanation for the appearance of de novo HLA‐specific antibodies directed against third party but not donor HLA.

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Anti-Human Leukocyte Antigen and Donor-Specific Antibodies Detected by Luminex Posttransplant Serve as Biomarkers for Chronic Rejection of Renal Allografts

Abstract: We confirmed that HLAab produced even late after transplantation are detrimental to graft outcome. DSA were proven to have a strong adverse impact on graft survival. The results indicate that a posttransplant HLAab monitoring routine could be appropriate to improve long-term results.

Cited by 325 publications

References 33 publications

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant

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

Transfer of HLA-Specific Allosensitization From a Highly Sensitized Deceased Organ Donor to the Recipients of Each Kidney

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