Should HLA Mismatch Acceptability for Sensitized Transplant Candidates Be Determined at the High-Resolution Rather Than the Antigen Level?

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

doi:10.1111/ajt.13167

Cited by 77 publications

(59 citation statements)

References 21 publications

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“…A data system, such as this one supporting the Canadian cPRA Calculator, with mandatory DQA, DPA, and DPB typing and the capability of including DQA, DPA, and DPB UA and A‐S‐Ab in VXM, where these are determined to be undesirable in transplant, may facilitate more efficient and equitable allocation of organs in patients with these UA with fewer unanticipated positive cell‐based crossmatches 13, 23. However, additional studies are needed to better understand the nature of allele‐specific responses, and moreover, the nature of epitope‐driven immunogenicity at the level of unique HLA proteins 24.…”

Section: Discussionmentioning

confidence: 99%

cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator

Tinckam

Liwski

Pochinco

et al. 2015

American Journal of Transplantation

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A calculated panel reactive antibody (cPRA) estimates the percentage of donors with unacceptable antigens (UA) for a recipient. cPRA may be underestimated in transplant candidates with UA to DQA, DPA, and DPB if these are not included in the calculation program. To serve the National Canadian Transplant Programs, a cPRA calculator was developed with complete molecular typing for all donors at HLA‐A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1, and DPB1, all resolved to serologic equivalents. The prevalence of UA at DQA, DPA and DPB was evaluated in a sensitized regional population. The impact of adding these additional UA to cPRA was calculated alone and in combination, and compared to the baseline cPRA for UA at A, B, C, DR, DR51/52/53, and DQ. Of 740 sensitized transplant candidates, 18% of total and 32% with cPRA≥95% had DQA UA. Twenty‐seven percent of total and 54% with cPRA≥95% had DPB UA. Of 280/740 subjects with these UA, 36/280 (13%) had cPRA increase of >20% when they were included, 7% increased cPRA to ≥80% and 6% to ≥95%. Inclusion of DQA, DPA, and DPB UA in Canadian cPRA calculations improves the accuracy of cPRA where these are relevant in allocation.

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Section: Discussionmentioning

confidence: 99%

cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator

Tinckam

Liwski

Pochinco

et al. 2015

American Journal of Transplantation

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“…Given these advancements, it has been proposed that high resolution typing may eventually be applied to non-sensitized candidates by adopting allele-based compatibility in order to avoid post-transplant sensitization. 40 In fact, recent studies suggest HLA allele-matching, and more specifically epitope-matching, results in better long term graft survival through decreased production of DSA compared to established HLA-matching. 41 Moreover, with antigen typing able to identify specificity at the allele level, alleles sharing epitopes to which a recipient has antibodies may be avoided.…”

Section: Genotyping Applications For Hematopoietic Stem Cell and Solimentioning

confidence: 99%

“…Otherwise a positive crossmatch would not have been predicted because the candidate had never been exposed to the allele in question. 40 …”

Section: Genotyping Applications For Hematopoietic Stem Cell and Solimentioning

confidence: 99%

Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience

Fasano¹,

Sullivan²,

Bray³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for the simultaneous detection of multiple human leukocyte antigens (HLA), human platelet antigens (HPA) and red blood cell (RBC) antigens. The development of high resolution molecular HLA typing has led to improved outcomes of unrelated hematopoietic stem cell transplants by better identifying suitable donors typed at the allele level for HLA-A, B, C, DRB1 and DQB1 antigens. In solid organ transplantation, the combination of high resolution HLA typing along with solid-phase antibody identification and the calculated PRA have shown to be of specific benefit to highly sensitized patients, and have resulted in significant reductions of incompatible crossmatches at the time of organ allocation. This database-driven combined HLA antigen/antibody testing has promoted the routine implementation of the virtual crossmatch, in which an electronic crossmatch is performed, and perhaps even obviates the need for a physical crossmatch. Additionally, DNA-based testing for RBC antigens provides as an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although there are many applications of RBC genotyping in various transfusion settings, it has arguably been most useful in the management of transfusion-dependent patients with sickle cell disease (SCD) and thalassemia to minimize alloimmunization. The availability of high-throughput RBC genotyping for both patients and large populations of donors, along with coordinated informatics systems to link patients’ antigen needs with available antigen-negative and/or rare blood-typed donors, offer promise toward improving the efficiency, reliability, and extent of RBC matching for this population.

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“…In the April issue of AJT, an editorial by Cecka et al (1) commented on our personal viewpoint article wherein we proposed that HLA mismatch acceptability for sensitized transplant candidates should be determined at highresolution levels (2). This editorial seems to express the view that HLA antigen-based testing be maintained as is despite its inherent deficiencies.…”

Section: To the Editormentioning

confidence: 99%

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

Duquesnoy

Gebel

Woodle

et al. 2015

American Journal of Transplantation

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Should HLA Mismatch Acceptability for Sensitized Transplant Candidates Be Determined at the High-Resolution Rather Than the Antigen Level?

Cited by 77 publications

References 21 publications

cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator

cPRA Increases With DQA, DPA, and DPB Unacceptable Antigens in the Canadian cPRA Calculator

Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience

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

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