HLA antibodies are associated with deterioration of kidney allograft function irrespective of donor specificity

Moos, Seraina von; Cippà, Pietro E; Breemen, Rob van; Mueller, Thomas

doi:10.1016/j.humimm.2020.10.010

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…These observations support the finding from a recent study that recipients with shared T-cell epitopes have higher early de novo DSA formation as compared to patients without shared T-cell epitopes ( 41 ). Our results may provide an explanation for why recipients with pre-transplant non-donor-specific HLA antibodies have a decreased graft survival ( 39 ) and diminished graft function ( 40 ) as compared to patients without any HLA antibodies. Possibly, recipients with non-donor-specific HLA antibodies have pre-transplant donor-HLA reactive CD4 + T-helper cells.…”

Section: Discussionmentioning

confidence: 77%

“…These shared T-cell epitopes may explain why recipients with pre-transplant non-donor-specific HLA antibodies experience have a decreased graft survival (39) and diminished graft function (40) as compared to patients without these HLA antibodies. A recent study investigated the effect of shared Tcell epitopes on the development of de novo DSA using the PIRCHE-II algorithm (41).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, the presence of T-cell epitopes that are shared between immunizing and donor HLA could potentially increase the risk of alloimmune reactions following transplantation. These shared T-cell epitopes may explain why recipients with pre-transplant non-donor-specific HLA antibodies experience have a decreased graft survival ( 39 ) and diminished graft function ( 40 ) as compared to patients without these HLA antibodies. A recent study investigated the effect of shared T-cell epitopes on the development of de novo DSA using the PIRCHE-II algorithm ( 41 ).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…24,25 Opelz et al 26 reported that 10-year graft survival was lower in recipients with PRA > 50% than in recipients with 0% PRA. Von Moos et al 27 found that PRA was associated with medium-term graft dysfunction compared with recipients without PRA in a follow-up visit.…”

Section: Discussionmentioning

confidence: 99%

“…32 Meanwhile, the relationship between PRA and deterioration of graft function is well documented. 3,27 Thus, we hypothesized that the reduction of PRA by IGU could improve the graft prognosis, reduce ABMR and prolong the graft survival.…”

Section: Discussionmentioning

confidence: 99%

Iguratimod reduces panel reactive antibody in high mismatched renal transplant recipients: One single‐center experience

Feng

Huang

Chen

et al. 2022

Clinical Transplantation

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Objective: To evaluate the clinical efficacy and safety of iguratimod (IGU) for reducing panel reactive antibody (PRA) in high-mismatched renal transplant recipients. Methods:Eligible recipients positive for PRAs who received or did not receive IGU treatment were enrolled. We retrospectively reviewed, collected, and analyzed statistically the clinical data of the recipients.Results: A total of 80 recipients were included for further analysis. After IGU was administered for 9 months, no significant difference was found in the change rates of donor specific antibodies between two groups. Meanwhile, the reduction in the PRAs in the IGU group was greater than that in the non-IGU group in anti-human leukocyte antigen (HLA) class I and class II, anti-HLA class I, anti-HLA class II, anti-HLA A, and anti-HLA DR antibodies. However, no differences were found in the anti-HLA B, anti-HLA Cw, anti-HLA DP, and anti-HLA DQ antibodies between the two groups.No serious adverse events were reported, and the incidence of adverse events was comparable between the two groups. Conclusion:PRA levels in high-mismatched renal transplant recipients were significantly reduced after the administration of IGU. The high safety of IGU was also determined.

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The impact of preformed and de novo HLA‐DP antibodies in renal transplantation, a meta‐analysis

Pan

You

Wang

et al. 2022

HLA

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The impact of preformed and de novo HLA-DP antibodies after renal transplantation remains controversial and unclear. To address the clinical relevance of HLA-DP antibodies on the outcomes in renal transplantation, we performed a random effect model meta-analysis through a systematic review from inception to December 31, 2021. The outcome was graft loss or acute rejection.Finally five articles were identified as our inclusion criteria. The study which reported 1166 patients included in the final meta-analysis of de novo HLA-DP antibodies after transplantation showed an increased risk of graft loss or acute rejection (OR = 3.6, 95% CI = 1.6-8.10, P = 0.002, I 2 = 52%). In the subgroup study, we established that patients with HLA-DP DSA after renal transplantation had a 8.85-fold increased risk of graft loss or acute rejection compared with patients without HLA-DP DSA (p = 0.003).While as for HLA-DP NDSA after renal transplantation, 2.73-fold increased risk of graft loss or acute rejection compared with patients without HLA-DP antibodies (p = 0.04). Besides, the studies which reported 487 patients included in the final meta-analysis of preformed HLA-DP antibodies did not show an increased risk of graft loss or acute rejection (OR = 4.55, 95% CI = 0.79-26.16, P = 0.09, I 2 = 57%). The results of our meta-analysis suggested that de novo HLA-DP antibodies especially de novo HLA-DP DSA had a significant deleterious impact on the renal transplant risk of graft loss or acute rejection, while preformed HLA-DP antibodies had a no significant deleterious impact on the risk. The routine detection of HLA-DP antibodies after renal transplantation seems to be very important and may be as one of noninvasive biomarker-guided risk stratification.

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HLA antibodies are associated with deterioration of kidney allograft function irrespective of donor specificity

Cited by 6 publications

References 30 publications

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

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

Iguratimod reduces panel reactive antibody in high mismatched renal transplant recipients: One single‐center experience

The impact of preformed and de novo HLA‐DP antibodies in renal transplantation, a meta‐analysis

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