High-Resolution HLA Typing for Sensitized Patients: Advances in Medicine and Science Require Us to Challenge Existing Paradigms

Duquesnoy, René J.; Gebel, Howard M.; Woodle, E. Steve; Nickerson, Peter; Baxter-Lowe, L.A.; Bray, Robert A.; Claas, Frans H.J.; Eckels, David D.; Friedewald, John; Fuggle, Susan V.; Gerlach, John; Fung, John J.; Kamoun, Malek; Middleton, Derek; Shapiro, Ron; Tambur, Anat R.; Taylor, Craig; Tinckam, Kathryn; Zeevi, Adriana

doi:10.1111/ajt.13376

Cited by 25 publications

(7 citation statements)

References 5 publications

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“…The role of HLA‐DQA and –DP‐specific antibodies has not been considered in this pilot study, although these are certainly relevant for the allocation of donor kidneys to HSPs. The same holds true for allele‐specific antibodies, which may be a reason to consider high‐resolution typing of patients and donors in a future Europe‐wide acceptable mismatch programme, especially as the frequency of the alleles may differ among the different European populations …”

Section: Discussionmentioning

confidence: 95%

Towards uniformity in the definition of acceptable mismatches for highly sensitized patients

Chen

Zoet

Roelen

et al. 2019

HLA

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The Eurotransplant (The Eurotransplant International Foundation) acceptable mismatch programme has been shown to be a successful tool to enhance transplantation of highly sensitized patients(HSPs). However, patients with rare HLA phenotypes in relation to the Eurotransplant donor population remain on the waiting list. EUROSTAM is an European Union funded project to explore the feasibility of a Europe‐wide acceptable mismatch programme enabling transplantation of HSPs with rare HLA phenotypes within their own organ exchange organization. The present study, which forms part of the EUROSTAM project, assesses the differences in the practices of the laboratories in different countries with respect to their HLA antibody profiling and risk adverseness. In the serum exchange exercises of 18 samples, a high level of variability has been shown in both assays and interpretation of results. In the data exchange exercise when all participants were given the same Luminex raw data for analysis, a high degree of consensus was reached where the median fluorescent intensity values of beads were <500 and >2000 for standard single antigen bead assays, or <500 and >5000 for assignment of acceptable mismatches. The risk adverseness analysis has showed distinct patterns of attitudes towards the perceived risks based on HLA antibody assay results, most probably influenced by the local protocols of the clinical transplant programme of each laboratory. In order to ensure fairness and maintain consistencies of organ exchange among partner transplant centres, a centralized facility will be instrumental for a uniform definition of acceptable mismatches.

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Section: Discussionmentioning

confidence: 95%

Towards uniformity in the definition of acceptable mismatches for highly sensitized patients

Chen

Zoet

Roelen

et al. 2019

HLA

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“…There is always a debate on the all important issue of whether HLA matching should be performed at low‐ or high‐resolution level and whether HLA‐C should also be considered in kidney allocation particularly for presensitized patients (Cecka et al ., ; Duquesnoy et al ., ). At least two recent studies have addressed this question and their data suggest that allele level matching especially of HLA‐DR and HLA‐C locus at high resolution significantly influences the outcome of renal allografts (Tran et al ., ; Heinold et al ., ).…”

Section: Do We Need Hla Matching At High Resolution At Hla‐c Locus?mentioning

confidence: 97%

“…More data needs to be accumulated to prove or disprove the above notion. To make the best use of an epitope‐based matching approach, high‐resolution matching is ideally required at all loci, that is HLA‐A, HLA‐B, HLA‐DR (DRB1), HLA‐DQB, HLA‐C, HLA‐DRB3/4/5, HLA‐DQA and HLA‐DP (Duquesnoy et al ., ).…”

Section: Do We Need Hla Matching At High Resolution At Hla‐c Locus?mentioning

confidence: 97%

Clinical and immunological relevance of antibodies in solid organ transplantation

Mehra

Baranwal

2016

Int J Immunogenetics

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The two important issues affecting recipients of solid organ transplants and of importance to immunologists are (i) sensitization of the recipient to HLA antigens and the resultant humoral immune response leading to the development of anti-HLA antibodies; and ii) development of robust assays for early detection of humoral rejection post-transplant. Evidence from several studies clearly indicates that presence of circulating anti-HLA antibodies especially donor specific leads to early graft loss and high titres of DSA may even lead to hyperacute or accelerated acute rejection. Long-term graft survival too is adversely affected by the presence of either pre- or post-transplant DSA. HLA matching status of the recipient - donor pair - is an important factor in the modulation of humoral response following transplantation and in a way affects de novo development of DSA. Data collected over the past decade clearly indicate significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA mismatches especially those on HLA-DR and HLA-C loci have wider implications on post-transplant graft survival. The presence of circulating anti-HLA antibodies leads to endothelial damage in the newly grafted organ through complement dependent or independent pathways. Although detection of C4d deposition in renal biopsies serves as an important indicator of humoral rejection, its absence does not preclude the presence of DSAs and humoral rejection, and hence, it cannot be relied upon in every case. The emergence of epitope-based screening for anti-HLA antibodies on Luminex platform with high degree of sensitivity has revolutionized the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral response to non-HLA antigens might also have a detrimental effect on allograft survival. High titres of such circulating antibodies may even lead to hyperacute rejection. Pre-emptive testing of solid organ recipients, especially kidney transplant recipients for anti-HLA and non-HLA antibodies and aggressive post-transplant monitoring of allograft function to detect DSAs using Luminex-based tests, is highly recommended.

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“…Bu durumda A*2407'ye karşı oluşan monoklonal antikor 70Q'ya spesifiktir ve sadece A*2407 ile reaksiyon vermektedir. 19,20 Ülkemizde de olduğu gibi birçok ülkede, böb-rek nakli öncesinde HLA Sınıf II moleküllerinden sadece DRB1 genleri tiplenmektedir. Ayrıca eplet programı ile alıcı ve donör arasında DRB1, DRB3, DRB4, DRB5 molekülleri karşılaştırıldığında DRB3, DRB4, DRB5 molekülleri alıcı donör çif-tinde uyumsuz eplet (tek ya da çift yamaları ifade ediyor) sayısı önemli miktarda etkilemektedir.…”

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“…Tablo 6'da da görüldüğü gibi, yüksek çözünürlükte doku tipleme testlerinin yapılması HLA epitoplarındaki eplet yapıları ile ilgili daha fazla bilgi verecektir. 25,26 Hasta X HLA tipi Aynı CREG olmasına rağmen uyumsuz tmm'ler Hasta Y HLA tipi Aynı CREG olmasına rağmen uyumsuz tmm'ler…”

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Investigation of Human Leucocyte Antigen Epitopes in Organ Transplantation: Review

Ayna¹,

Pirim²

2017

Turkiye Klinikleri J Intern Med

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High-Resolution HLA Typing for Sensitized Patients: Advances in Medicine and Science Require Us to Challenge Existing Paradigms

Cited by 25 publications

References 5 publications

Towards uniformity in the definition of acceptable mismatches for highly sensitized patients

Towards uniformity in the definition of acceptable mismatches for highly sensitized patients

Clinical and immunological relevance of antibodies in solid organ transplantation

Investigation of Human Leucocyte Antigen Epitopes in Organ Transplantation: Review

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