A New HLA Allocation Procedure of Kidneys From Deceased Donors in the Current Era of Immunosuppression

Broeders, Nilüfer; Racapé, Judith; Hamade, Anwar; Massart, Annick; Hoang, Anh Dung; Mikhalski, Dimitri; Moine, Alaín Le; Vereerstraeten, Pierre

doi:10.1016/j.transproceed.2014.12.018

Cited by 11 publications

(9 citation statements)

References 15 publications

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“…One of the main factors determining a successful outcome of kidney transplantation is the compatibility between the donor and recipient for human leukocyte antigen (HLA) genes of the major histocompatibility complex (MHC), particularly those of class II [3, 4]. The complex immunological mechanisms underlying acute and chronic rejection involve both humoral and cell-mediated immunity.…”

Section: Introductionmentioning

confidence: 99%

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

et al. 2017

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BackgroundKidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity.Methods and findingsA cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls.Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group.The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate.ConclusionsKIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.

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Section: Introductionmentioning

confidence: 99%

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

et al. 2017

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“…Polymorphisms in HLA, especially HLA-A, -B, and -DR loci, are important biological barriers to a successful transplantation. [ 3 , 21 ] As closely HLA-matched graft is less likely to be recognized and rejected, HLA mismatching has a substantial impact on prolongation of graft survival. [ 22 ] Quantitative assessments of the effect of HLA mismatching on heart, liver, umbilical cord blood, and hematopoietic stem cell transplantation, have already been reported.…”

Section: Discussionmentioning

confidence: 99%

“…With the emergence of potent immunosuppressive agents that steadily improved graft survival rates, the impact of HLA compatibility seems to be minimized. [ 3 , 23 ] Different regions or countries (European, US, UK, Australia, Israel, etc.) reported different kidney allocation guideline recommendations based on HLA-compatibility.…”

Section: Discussionmentioning

confidence: 99%

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The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation

Shi

Han²,

Ding³

2017

Medicine

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Background:Human leukocyte antigen (HLA) was important biological barrier to a successful transplantation. Quantitative evaluations of the effect of HLA mismatching on heart, liver, umbilical cord blood, and hematopoietic stem cell transplantation, have previously been reported. In new era of immunosuppression, the reported magnitude effect of HLA mismatching on survival outcomes of kidney transplantation was controversial. In addition, the current kidney allocation guideline recommendations in different countries were inconsistent in term of HLA mismatching. We undertake this study to conduct a systematic review and meta-analysis to assess the magnitude effect of HLA mismatching in adult kidney transplantation, with a particular focus on graft survival and mortality.Methods:The present systematic review and meta-analysis protocol was conducted following the Meta-analysis of Observational Studies in Epidemiology protocol (MOOSE-P) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P). PubMed, EMBASE, Cochrane library Database will be searched without language restriction. Studies fulfill the following criteria will be eligible: included study cohorts comprising adult recipients; reported the association between HLA mismatching (per mismatches or HLA-A, -B, -DR mismatches) and posttransplant survival outcomes; provided effect estimates of hazard ratios (HRs) with 95% confidence interval (CIs). The incidence of measured outcomes was defined according to the European Renal Best Practice Transplantation Guidelines and Kidney Disease: Improving Global Outcomes Guidelines.Results:This study will quantitatively assess the association of HLA per mismatches, DR-antigen mismatches, A-antigen mismatches, and B-antigen mismatches with survival outcomes of overall graft failure, death-censored graft failure, all-cause mortality, and mortality with a functioning graft.Conclusion:This study will determine the issues on what extent HLA compatibility influenced recipient and graft survival and which HLA antigen plays a more important role in kidney transplantation.Systematic review registration:PROSPERO CRD42017071894.

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“…The best survival of 92% was with mismatches limited to 1 A or B antigen. Freedom of graft failure due to immunologic causes was 96.5% for mismatches limited to 1 A or B antigen and no DR mismatch and was 89–91% for all other mismatch groups (7). …”

Section: Effect Of Hla Matching/mismatching On Outcomesmentioning

confidence: 99%

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

Zachary

Leffell

2016

Front. Immunol.

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HLA matching provides numerous benefits in organ transplantation including better graft function, fewer rejection episodes, longer graft survival, and the possibility of reduced immunosuppression. Mismatches are attended by more frequent rejection episodes that require increased immunosuppression that, in turn, can increase the risk of infection and malignancy. HLA mismatches also incur the risk of sensitization, which can reduce the opportunity and increase waiting time for a subsequent transplant. However, other factors such as donor age, donor type, and immunosuppression protocol, can affect the benefit derived from matching. Furthermore, finding a well-matched donor may not be possible for all patients and usually prolongs waiting time. Strategies to optimize transplantation for patients without a well-matched donor should take into account the immunologic barrier represented by different mismatches: what are the least immunogenic mismatches considering the patient’s HLA phenotype; should repeated mismatches be avoided; is the patient sensitized to HLA and, if so, what are the strengths of the patient’s antibodies? This information can then be used to define the HLA type of an immunologically optimal donor and the probability of such a donor occurring. A probability that is considered to be too low may require expanding the donor population through paired donation or modifying what is acceptable, which may require employing treatment to overcome immunologic barriers such as increased immunosuppression or desensitization. Thus, transplantation must strike a balance between the risk associated with waiting for the optimal donor and the risk associated with a less than optimal donor.

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A New HLA Allocation Procedure of Kidneys From Deceased Donors in the Current Era of Immunosuppression

Cited by 11 publications

References 15 publications

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

KIR and their HLA Class I ligands: Two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation

The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation

HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act

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