Critical evaluation of a possible role of HLA epitope matching in kidney transplantation

Sahin, Gizem Kumru; Unterrainer, Christian; Süsal, Caner

doi:10.1016/j.trre.2020.100533

Cited by 26 publications

(22 citation statements)

References 49 publications

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“…Moreover, the same antigenic epitope can be present on different alleles, which further complicates the evaluation of compatibility. To improve the precision of matching between donor and recipient and the knowledge on HLA incompatibilities that are relevant for rejection of kidney allografts, several theoretical and experimentbased algorithms have been developed (7)(8)(9)(10)(11). The Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-II) algorithm is one of these promising theoretical approaches and matching based on this algorithm was shown to have potential to improve graft survival (12).…”

Section: Introductionmentioning

confidence: 99%

Can PIRCHE-II Matching Outmatch Traditional HLA Matching?

Unterrainer

Döhler

Niemann³

et al. 2021

Front. Immunol.

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We analyzed in a cohort of 68,606 first deceased donor kidney transplantations reported to the Collaborative Transplant Study whether an epitope-based matching of donor-recipient pairs using the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II) is superior to currently applied HLA antigen matching. PIRCHE-II scores were calculated based on split antigen HLA-A, -B, -DRB1 typing and adjusted to the 0–6 range of HLA mismatches. PIRCHE-II scores correlated strongly with the number of HLA mismatches (Spearman ρ = 0.65, P < 0.001). In multivariable analyses both parameters were found to be significant predictors of 5-year death-censored graft loss with high prognostic power [hazard ratio (HR) per adjusted PIRCHE-II score = 1.102, per HLA mismatch = 1.095; z-value PIRCHE-II: 9.8, HLA: 11.2; P < 0.001 for both]. When PIRCHE-II scores and HLA mismatches were analyzed simultaneously, their predictive power decreased but remained significant (PIRCHE-II: P = 0.002; HLA: P < 0.001). Influence of PIRCHE-II was especially strong in presensitized and influence of HLA mismatches in non-sensitized recipients. If the level of HLA-incompatibility was low (0–3 mismatches), PIRCHE-II scores showed a low impact on graft survival (HR = 1.031) and PIRCHE-II matching did not have additional significant benefit (P = 0.10). However, if the level of HLA-incompatibility was high (4–6 mismatches), PIRCHE-II improved the positive impact of matching compared to applying the traditional HLA matching alone (HR = 1.097, P = 0.005). Our results suggest that the PIRCHE-II score is useful and can be included into kidney allocation algorithms in addition to HLA matching; however, at the resolution level of HLA typing that is currently used for allocation it cannot fully replace traditional HLA matching.

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Section: Introductionmentioning

confidence: 99%

Can PIRCHE-II Matching Outmatch Traditional HLA Matching?

Unterrainer

Döhler

Niemann³

et al. 2021

Front. Immunol.

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“…The degree of HLA matching at the antigen level has been observed to be associated with graft survival (9). However, several studies have shown that epitope-based HLA matching could be more effective than antigen-based HLA matching (10)(11)(12)(13)(14), as antigen-based HLA matching has some limitations. For example, a mismatched HLA allele may lack immunogenic epitopes capable of inducing an alloimmune response.…”

Section: Introductionmentioning

confidence: 99%

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation

et al. 2021

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CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.

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“…(2) Inference tools infer the 2F‐HR genotypes from the LR results based on the observed HLA allelic frequencies and haplotypes in different ethnic populations and are often used in the transplant field 11‐14 . The possibility to estimate the 2F‐HR HLA data brings additional confusion in the discussion about the clinical value of 2F‐HR genotyping methods in the field of solid organ transplantation 15 . Although it is possible to obtain the 2F‐HR genotypes correctly from the LR genotypes for some individuals, 16 it remains unknown whether such inference affects calculations of donor‐recipient eplet incompatibility.…”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13][14] The possibility to estimate the 2F-HR HLA data brings additional confusion in the discussion about the clinical value of 2F-HR genotyping methods in the field of solid organ transplantation. 15 Although it is possible to obtain the 2F-HR genotypes correctly from the LR genotypes for some individuals, 16 it remains unknown whether such inference affects calculations of donor-recipient eplet incompatibility.…”

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confidence: 99%