Results and reflections from the PROfiling Consortium on Antibody Repertoire and Effector functions in kidney transplantation: A mini‐review

Kamburova, Elena G.; Hoitsma, Andries J.; Claas, Frans H.J.; Otten, Henny G.

doi:10.1111/tan.13581

Cited by 9 publications

(7 citation statements)

References 79 publications

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“…In particular, monitoring of pre-transplant as well as de novo DSA has become more widespread with an increasing number of studies focusing on the relationship between the presence of DSA and incidence of ABMR 42 – 45 . Although ABMR is often accompanied by the presence of DSA, this is not always the case, nor is the presence of DSA associated with adverse outcomes in all kidney transplant recipients 46 – 48 . While much remains unknown about the individual contributions of these risk factors, it is clear that donor-reactive immune memory can be difficult to detect and difficult to inhibit.…”

Section: Discussionmentioning

confidence: 99%

Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection

Rojas

Gelder

Kuiper

et al. 2021

Sci Rep

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Pre-transplant screening focuses on the detection of anti-HLA alloantibodies. Previous studies have shown that IFN-γ and IL-21 producing T cells are associated with the development of acute rejection (AR). The aim of this study, was to assess whether pre-transplant donor-reactive T cells and/or B cells are associated with increased rejection risk. Samples from 114 kidney transplant recipients (transplanted between 2010 and 2013) were obtained pre-transplantation. The number of donor-reactive IFN-γ and IL-21 producing cells was analyzed by ELISPOT assay. The presence of donor specific antibodies (DSA) was also determined before transplantation. Numbers of donor-reactive IFN-γ producing cells were similar in patients with or without AR whereas those of IL-21 producing cells were higher in patients with AR (p = 0.03). Significantly more patients with AR [6/30(20%)] had detectable DSA compared to patients without AR [5/84(5.9%), p = 0.03]. Multivariate logistic regression showed that donor age (OR 1.06), pre-transplant DSA (OR 5.61) and positive IL-21 ELISPOT assay (OR 2.77) were independent predictors of an increased risk for the development of AR. Aside from an advanced donor-age and pre-transplant DSA, also pre-transplant donor-reactive IL-21 producing cells are associated with the development of AR after transplantation.

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Section: Discussionmentioning

confidence: 99%

Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection

Rojas

Gelder

Kuiper

et al. 2021

Sci Rep

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“…Preliminary data indicate that patients having two or more pre‐transplant DESAs, defined by taking all eplets listed in the HLA Eplet Registry into account, showed inferior graft survival compared with patients with zero to two DESAs 41 . However, 10‐year graft survival rate is ~50% in patients with ≥2 DESA.…”

Section: Discussionmentioning

confidence: 99%

Determination of the clinical relevance of donor epitope‐specific HLA‐antibodies in kidney transplantation

Kardol‐Hoefnagel,

Senejohnny,

Kamburova

et al. 2024

HLA

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In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex‐defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs. irrelevant HLA antibodies. To evaluate which donor epitope‐specific HLA antibodies (DESAs) are clinically important in kidney graft survival, relevant and irrelevant DESAs were discerned in a Dutch cohort of 4690 patients using Kaplan–Meier analysis and tested in a cox proportional hazard (CPH) model including nonimmunological variables. Pre‐transplant DESAs were detected in 439 patients (9.4%). The presence of certain clinically relevant DESAs was significantly associated with increased risk on graft loss in deceased donor transplantations (p < 0.0001). The antibodies recognized six epitopes of HLA Class I, 3 of HLA‐DR, and 1 of HLA‐DQ, and most antibodies were directed to HLA‐B (47%). Fifty‐three patients (69.7%) had DESA against one donor epitope (range 1–5). Long‐term graft survival rate in patients with clinically relevant DESA was 32%, rendering DESA a superior parameter to classical DSA (60%). In the CPH model, the hazard ratio (95% CI) of clinically relevant DESAs was 2.45 (1.84–3.25) in deceased donation, and 2.22 (1.25–3.95) in living donation. In conclusion, the developed model shows the deleterious effect of clinically relevant DESAs on graft outcome which outperformed traditional DSA‐based risk analysis on antigen level.

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“…An additional algorithm, Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-II), predicts in silico the number of HLA mismatch-derived epitopes that can be presented to helper T cells [ 24 ]. Nonetheless, the up-to-date existing data are still poor and more research is needed before wider application is feasible [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

An Approach to Identify HLA Class II Immunogenic Epitopes in the Greek Population through Machine Learning Algorithms

Fylaktou

Λιούλιος

Tarassi

et al. 2022

JCM

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Current pre-transplantation routine matching involves serum anti-HLA antibodies quantification but cannot always preclude unfavorable graft outcomes. Epitope-based matching is proposed as a more precise approach, but to date no epitope-matching algorithm provides a satisfactory predictive tool for transplantation outcomes. In this study, anti-HLA-II loci responses from 1748 patients were analyzed with unsupervised machine learning algorithms, namely principal component analysis (PCA) and antigenic distances, projected as dendrograms. PCA for anti-HLA-DR anti-bodies revealed three main clusters of responses: anti-HLA-DR51 combined with anti-HLA-DRB1*01, anti-HLA-DR52 combined with anti-HLA-DRB1*08 and anti-HLA-DR53 combined with anti-HLA-DRB1*10. The dendrogram for anti-HLA-DR confirmed the pattern and showed further bisection of each cluster. Common epitopes present exclusively in all HLA molecules of each cluster were determined following the HLA epitope registry. Thus, we propose that 19 out of 123 HLA-DR epitopes are those that mainly lead anti-HLA-DR responses in the studied population. Likewise, we identified 22 out of 83 epitopes responsible for anti-HLA-DQ and 13 out of 62 responsible for anti-HLA-DP responses. Interpretation of these results may elucidate mechanisms of interlocus cross-reactivity, providing an alternative way of estimating the significance of each epitope in a population and thus suggesting a novel strategy towards optimal donor selection.

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Results and reflections from the PROfiling Consortium on Antibody Repertoire and Effector functions in kidney transplantation: A mini‐review

Cited by 9 publications

References 79 publications

Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection

Pre-transplant donor-reactive IL-21 producing T cells as a tool to identify an increased risk for acute rejection

Determination of the clinical relevance of donor epitope‐specific HLA‐antibodies in kidney transplantation

An Approach to Identify HLA Class II Immunogenic Epitopes in the Greek Population through Machine Learning Algorithms

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