Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report

Tambur, Anat R.; Campbell, Patricia; Chong, Anita S.; Feng, Sandy; Ford, Mandy L.; Gebel, Howard M.; Gill, Ronald G.; Kelsoe, Garnett; Kosmoliaptsis, Vasilis; Mannon, Roslyn B.; Mengel, Michael; Reed, Elaine F.; Valenzuela, Nicole M.; Wiebe, Chris; Dijke, I. Esmé; Sullivan, Harold C.; Nickerson, Peter

doi:10.1111/ajt.15937

Cited by 93 publications

(73 citation statements)

References 129 publications

(228 reference statements)

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“…This should not be confused with using eplet mismatch load in matching algorithms or for assignment of immunogenicity. In fact, the Sensitization in Transplantation: Assessment of Risk (STAR) 2017 and the STAR 2019 workgroups clearly stated that eplets should not be confused with epitopes, and eplet mismatch load should not be confused with assignment of immunogenicity burden 16,17 . We have recently demonstrated this point in a unique cohort of patients who were transplanted across 2 HLA‐DQ mismatches but developed antibodies to only 1 of the mismatched DQ.…”

Section: Discussionmentioning

confidence: 91%

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation

Engen

Jedraszko

Conciatori

et al. 2021

American Journal of Transplantation

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High-resolution human leukocyte antigen (HLA) typing is a time-consuming and expensive process that is typically reserved for hematopoietic stem cell transplantion. Solid organ transplantation currently relies on low-or intermediate-resolution antigen reporting, but recent publications on the value of molecular mismatch analysis highlight the potential role for high-resolution HLA typing in support of clinical decision-making and research in solid organ transplantation. In the absence of available high-resolution typing, investigators have resorted to imputation, focusing on 3 lines of study: (1) assessment of molecular mismatch load as a guide to stratify patients' risk for developing de

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Section: Discussionmentioning

confidence: 91%

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation

Engen

Jedraszko

Conciatori

et al. 2021

American Journal of Transplantation

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“…14 Although molecular mismatch loads are more precise to predict an immune response than conventional HLA mismatch counts, the next logical step to further improve this concept requires the assignment of an "immunogenicity tag" to each individual eplet or amino acid configuration. 15,16 Unfortunately, this task is complex and still in its infancy. The initial approach defined the immunogenicity of eplets by the frequency of antibody responses against them in transplant recipients (reviewed in Reference 17).…”

mentioning

confidence: 99%

Development of an immunogenicity score for HLA‐DQ eplets: A conceptual study

Schawalder

Hönger

Kleiser

et al. 2020

HLA

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Eplets are defined as distinct amino acid configurations on the surface of HLA molecules. The aim of this study was to estimate the immunogenicity of HLA-DQ eplets in a cohort of 221 pregnancies with HLA-DQ mismatches. We defined the immunogenicity of an eplet by the frequency of antibody responses against it. Around 90% of all listed DQB1 or DQA1 eplets were at least five times mismatched and thus included for the calculation of their immunogenicity. The DQB1 eplets with the five highest immunogenicity scores were 55PP, 52PR, 52PQ, 85VG and 45EV; 25% of all DQB1 eplets were not reacting. The DQA1 eplets with the five highest immunogenicity scores were 25YS, 47QL, 55RR, 187T and 18S; 17% of all DQA1 eplets were not reacting. The immunogenicity score had a slightly higher area under the curve to predict development of childspecific antibodies than various molecular mismatch scores (eg, eplet mismatch load, amino acid mismatch load). Overlapping eplets were identified as a barrier to unambiguously assign the immunogenicity score based on HLA antibody reaction patterns. In this conceptual study, we explored the immunogenicity of HLA-DQ eplets and created a map of potentially immunogenic regions on HLA-DQ molecules, which requires validation in clinical transplant cohorts.

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“…As a consequence, HLA laboratories must incorporate multiple laboratory tests and analyses with information about each individual to ensure that the correct information regarding immunological risk is provided for each patient. Similar approaches were recommended in working group report of Sensitization in Transplantation: Assessment of Risk (STAR) (77). Cw 81 93 91 31 14 27 30 28 88 95 21 13 24 29 13 100 82 89 76 94 50 80 ------33 -68 34 25 33 --66 68 66 26 69 ---------------------------------------------…”

Section: Discussionmentioning

confidence: 93%

Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff

McCaughan

Tinckam

2019

Hepatobiliary Surg. Nutr

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Human leukocyte antigen (HLA) compatibility is very important for successful transplantation of solid organs. In this paper, we focused on the humoral arm of immunity in the clinical setting of organ transplantation: how HLA antibodies develop, how they can be detected, and what they can do to injure organ transplants. Specifically, we explore the technical perspectives of detecting donor-specific antibodies (DSA) in HLA laboratories, and use real-life clinical cases to explain the principles. Currently there are many tools in our HLA antibody detection toolbox: conventional cytotoxicity cross match, flow cross match, and solid phase assays using beads conjugated with single or multiple HLA antigens. Single antigen bead (SAB) assay is the most sensitive tool available for detecting HLA antibodies and assessing the immunological risk for organ transplant. However, there are intrinsic limitations to solid-phase assays and they are prone to both false negativity and importantly, false positivity. Denatured antigens on single antigen beads might be the most prominent source of false positive reactivity, and may have been underestimated by many HLA experts. No single assay is perfect and therefore multiple methods, including the less sensitive assays, should be employed to determine the clinical relevance of detected HLA antibodies. Thoughtful process, including knowledge of HLA systems, cross reactivity, epitopes, and the patient's clinical history should be employed to correctly interpret data. The clinical team should work closely with HLA laboratories to ensure accurate interpretation of information and optimal management of patients before and after organ transplantation.

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Sensitization in transplantation: Assessment of risk (STAR) 2019 Working Group Meeting Report

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 93 publications

References 129 publications

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation

Development of an immunogenicity score for HLA‐DQ eplets: A conceptual study

Detecting donor-specific antibodies: the importance of sorting the wheat from the chaff

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