Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant

Jeon, Hee Jung; Lee, Jae Ghi; Kim, Kwangsoo; Jang, Jinho; Han, Sung Won; Choi, Joonmyung; Ryu, Jung Hwa; Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Jae Woo; Ishida, Hideyuki; Park, Jae Berm; Lee, Sang Ho; Ahn, Curie; Yang, Jaeseok

doi:10.1111/ajt.15553

Cited by 8 publications

(11 citation statements)

References 49 publications

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“…The issue on the frequency of HLA antibody monitoring remains to be clarified. At the same time, innovative methods including high throughput technology and bioinformatics are currently in use in an effort to identify a biomarker for early detection of ABMR (30)(31)(32). Preventive measures are currently considered to be more likely to provide superior patient care when compared to the impact of therapeutic or preemptive strategies.…”

Section: Discussionmentioning

confidence: 99%

Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study

et al. 2020

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Risk prediction of de novo donor specific antibody (DSA) would be very important for long term graft outcome after organ transplantation. The purpose of this study was to elucidate the association of eplet mismatches and predicted indirectly recognizable HLA epitopes (PIRCHE) scores with de novo DSA production. Our retrospective cohort study enrolled 691 living donor kidney transplantations. HLA-A, B, DRB and DQB eplet mismatches and PIRCHE scores (4 digit of HLA-A, B, DR, and DQ) were determined by HLA matchmaker (ver 2.1) and PIRCHE-II Matching Service, respectively. Weak correlation between eplet mismatches and PIRCHE scores was identified, although both measurements were associated with classical HLA mismatches. Class II (DRB+DQB) eplet mismatches were significantly correlated with the incidence of de novo class II (DR/DQ) DSA production [8/235 (3.4%) in eplet mismatch ≤ 13 vs. 92/456 (20.2%) in eplet mismatch ≥ 14, p < 0.001]. PIRCHE scores were also significantly correlated with de novo class II DSA production [26/318 (8.2%) in PIRCHE ≤ 175 vs. 74/373 (19.8%) in PIRCHE ≥ 176, p < 0.001]. Patients with low levels of both class II eplet mismatches and PIRCHE scores developed de novo class II DSA only in 4/179 (2.2%). Analysis of T cell and B cell epitopes can provide a beneficial information on the design of individualized immunosuppression regimens for prevention of de novo DSA production after kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study

et al. 2020

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“…Peripheral blood transcriptomic analysis allowed to build a classification model capable of discriminating ABMR from accommodation in ABO-incompatible kidney transplants [ 89 ].…”

Section: Armentioning

confidence: 99%

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

Quaglia

Merlotti

Guglielmetti

et al. 2020

IJMS

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New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

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“…Currently, the diagnosis of acute AMR still relies on kidney graft biopsy. To minimize the diagnosis risk, Jeon et al 55 developed a 5‐gene classification model including COX7A2L , CD69 , CD114 , CFD , and FOXJ3 to discriminate accommodation and early AMR in ABO‐ILKT based on the peripheral blood transcriptome analysis, which was validated in an independent external cohort with 92.7% sensitivity, 85.7% specificity, and 91.7% accuracy. The model is promising as a screening test; however, its efficacy remains to be confirmed by larger‐scale trials.…”

Section: Current Proceduresmentioning

confidence: 99%

ABO‐incompatible living kidney transplantation

Cen

Wang

Kong

et al. 2020

Clinical Transplantation

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To date, kidney transplantation is the optimal replacement therapy for most patients with end-stage renal disease (ESRD) because of a higher survival rate and decreased cost. 1,2 However, many patients have to undergo dialysis for many years owing to the growing kidney transplantation waiting list and organ scarcity. To overcome the shortage of available organs, various strategies have been established. Apart from increased deceased donor and marginal kidney use, more attention has been focused on expanding the living donor pool, mainly including crossing the HLA/ABO barrier and kidney paired donation (KPD). ABO-incompatible living kidney transplantation (ABO-ILKT) was once believed to be the absolute contraindication to kidney transplantation because of hyperacute humoral rejection and early graft loss. 3 However, with the introduction of antibody removal methods and evolving immunosuppressive protocols, ABO-ILKT currently is conducted widely with graft survival equivalent to that of ABOcompatible living kidney transplantation (ABO-CLKT). 4 Currently, more than a quarter and one third of the living donor kidney transplantation in Germany and Japan, respectively, are ABO-ILKT. 5,6 Instead of overcoming ABO incompatibility, the concept of KPD is to avoid the incompatibility barrier. KPD has been performed in many countries, including the Netherlands, the United States, Canada, Australia, the United Kingdom, Turkey, and India and has the advantages of low immunological risk, cost-effectiveness, and avoidance of desensitization complications, such as infection and bleeding. 5 Nonetheless, these limitations should be considered because of a long waiting period, blood group imbalance, geographical distance, and highly sensitized patients accumulating in KPD registries and

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Peripheral blood transcriptome analysis and development of classification model for diagnosing antibody-mediated rejection vs accommodation in ABO-incompatible kidney transplant

Cited by 8 publications

References 49 publications

Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study

Analysis of T and B Cell Epitopes to Predict the Risk of de novo Donor-Specific Antibody (DSA) Production After Kidney Transplantation: A Two-Center Retrospective Cohort Study

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

ABO‐incompatible living kidney transplantation

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