First report on the antibody verification of HLA-DR, HLA-DQ and HLA-DP epitopes recorded in the HLA Epitope Registry

Duquesnoy, René J.; Marrari, Marilyn; Tambur, Anat R.; Mulder, Arend; Sousa, Luiz Cláudio Demes da Mata; Silva, Adalberto Socorro da; Monte, Semíramis Jamil Hadad do

doi:10.1016/j.humimm.2014.09.012

Cited by 75 publications

(61 citation statements)

References 77 publications

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“…We would not assume that DQA, DPA and DPB frequencies in the OPTN donor population are same as the Canadian donor population without actual typing data, and more rigorous population genetic analysis; however, recent paired exchange data using a cPRA calculator from the National Kidney Registry donor pool that did include DPB typing suggest that antibodies to at least DPB affect US‐based cPRA calculations comparably to the impact demonstrated in our study 19. Interpretation of DPB typing and UA may be further limited by the absence of known robust DPA/DPB haplotype associations, as well as the limited polymorphism at the DPB locus (with broad antibody specificities driven by a potentially limited number of epitope sites alone or in combination) 22 and evolution of our simplified approach to impact of DPB on cPRA requires more rigorous studies.…”

Section: Discussionmentioning

confidence: 49%

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: 49%

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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“…Many more eplets are predicted by HLAMatchmaker that have not yet been verified by antibody binding. The international Registry of Antibody Defined HLA Epitopes developed a website (http://www.epregistry.com.br) to record all possible HLA epitopes, denoting those that have been antibody verified [11, 12]. This registry contains 5 databases, HLA-ABC, HLA-DRB, HLA-DQ, HLA-DP, and MICA.…”

Section: Epitopes In Hla Matchingmentioning

confidence: 99%

“…The registry does not consider epitopes defined by specific α / β parings but determines epitope specificity solely by the β -chain [12]. However, Tambur et al provide evidence that specific α / β -chain parings can determine a DQ epitope, not either chain in isolation.…”

Section: Epitopes In Hla Matchingmentioning

confidence: 99%

The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies

Filippone

Farber

2016

Journal of Immunology Research

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Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA mismatches. Determination of the pathogenicity of alloantibodies is evolving. Potential features include antibody strength (as assessed by antibody titer or, more commonly and inappropriately, mean fluorescence intensity) and ability to fix complement (in vitro by C1q or C3d assay or by IgG subclass analysis). Technical issues with the use of solid phase assays are also of prime importance, such as denaturation of HLA antigens and manufacturing and laboratory variability. Questions and controversies remain, and here we review new relevant data.

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“…During the past 2 decades, many investigators, notably Paul Terasaki's group, have confirmed unique HLA epitopes defined by antibodies and three recent publications list 97 HLA-ABC, 50 HLA-DR, -DQ, -DP and 21 MICA antibody-verified epitopes recorded so far in the International Registry of HLA Epitopes at http://www. epregistry.com.br (3)(4)(5).…”

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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First report on the antibody verification of HLA-DR, HLA-DQ and HLA-DP epitopes recorded in the HLA Epitope Registry

Cited by 75 publications

References 77 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

The Humoral Theory of Transplantation: Epitope Analysis and the Pathogenicity of HLA Antibodies

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

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