The Association Between Broad Antigen HLA Mismatches, Eplet HLA Mismatches and Acute Rejection After Kidney Transplantation

Nguyen, Hung Thanh; Wong, Germaine; Chapman, Jeremy R.; McDonald, S.; Coates, P. Toby; Watson, Narelle; Russ, Graeme R.; D’Orsogna, Lloyd; Lim, Wai H.

doi:10.1097/txd.0000000000000632

Cited by 25 publications

(23 citation statements)

References 24 publications

(30 reference statements)

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“…Lachmann et al 9 showed in a cohort of 2787 adults with a kidney transplantation, with a mean follow‐up of 7.2 years that the occurrence of DSA (16%) is dependent on the eplet load, more eplets mismatches, higher incidents of DSA. In a cohort of 3449 adults observed for a similar period of time (3.4 years the median follow‐up), Nguyen et al 10 showed that 18% of the patients developed DSA and the median eplet load was 22.8 (higher than in our study) and the patients were evaluated only for HLA DR typing. In pediatric transplantation, we found two papers reporting eplet match in kidney transplantation.…”

Section: Discussionsupporting

confidence: 46%

Eplet incompatibility in pediatric renal transplantation

Dubois

Ranchin

Sellier‐Leclerc

et al. 2020

Pediatric Transplantation

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Eplet incompatibility appears to be a better predictor of the de novo appearance of DSA post‐Tx than HLA antigen matching in adults. We evaluated the HLA Matchmaker® software (version 2.1) in our pediatric cohort to predict the appearance of DSA post‐Tx. We included 70 pediatric patients (26 girls, 10 living donors, mean age 11.2 ± 3.9 years) after a first R‐Tx (January 2010‐August 2016), without prior immunization, having complete HLA typing (A, B, C, DRB1 and DQB1) and DSA follow‐up for at least one year. The mean of HLA and eplet incompatibilities was 4.7 ± 1.3 and 15.5 ± 6.1, respectively, with a correlation coefficient r2 between these two variables of 0.34 (P < .001). The eplet load was 12.8 ± 5.0 in living donors vs 15.9 ± 6.2 in deceased donors (P = NS), 12.6 ± 6.1 in preemptive R‐Tx (n = 14) vs 16.3 ± 5.9 for non‐preemptive R‐Tx (P = .04). Seven patients (10%) developed DSA during the 3.5 ± 1.2 years post‐Tx. The eplet load was 13.7 ± 5.5 for those who developed DSA vs 15.7 ± 6.1 for the others (P = NS). In our single‐center series of pediatric R‐Tx with good HLA matching and lower eplet load than previously published series, eplet incompatibilities do not predict the development of DSA. The question of the HLA matching requirement and the daily interest of the HLA Matchmaker® software to help select the grafts remain open.

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Section: Discussionsupporting

confidence: 46%

Eplet incompatibility in pediatric renal transplantation

Dubois

Ranchin

Sellier‐Leclerc

et al. 2020

Pediatric Transplantation

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“…In fact, it is well documented that HLA antibodies can be generated against an allele with only a single amino acid difference, such as in cases of allele level antibodies . Moreover, multiple cutoff values for eplet mismatch load are reported in different studies . Indeed, the data presented here demonstrate this exact limitation.…”

Section: Discussionmentioning

confidence: 76%

“…It is notable that only minor variations were found when comparing the ability of these different approaches to predict poor graft outcome (correlation ranging between R 2 of .85‐.96) . In addition, when different patient populations were studied (eg, pediatric vs adult; kidney vs lung), different cutoff values were reported, indicating the need to determine appropriate cutoff values for center‐specific populations before adopting any of these approaches. Significantly, in each of the cohorts, a high mismatch score was not universally associated with de novo HLA‐DSA generation or rejection and vice versa, suggesting that factors beyond number of mismatches play a role in determining the immunogenicity and antigenicity of donor/recipient mismatches.…”

Section: Introductionmentioning

confidence: 99%

The quest to decipher HLA immunogenicity: Telling friend from foe

Tambur

McDowell

Hod-Dvorai

et al. 2019

American Journal of Transplantation

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| INTRODUC TI ONAdvances in HLA typing and HLA antibody testing over the past two decades transformed our ability to assess donor/recipient compatibility in the context of organ transplantation. Beginning from serologic donor/recipient HLA matching through emphasis on avoidance of preformed donor-specific HLA antibodies (DSAs), current approaches delve into amino acid sequences of HLA alleles, assessing the so-called molecular mismatch between donor and recipient, using one or more of the currently available tools: HLAMatchmaker, [1][2][3][4] Amino-Acid comparison, Electrostatic Mismatch Score (EMS 5-7 ), or PIRCHE-Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA-Class II antigens. 8-10 A short description of each method is provided in the supplemental material.It is notable that only minor variations were found when comparing the ability of these different approaches to predict poor graft outcome (correlation ranging between R 2 of .85-.96). 8,11 In addition, when different patient populations were studied (eg, pediatric vs adult; kidney vs lung), different cutoff values were reported, 12-19 indicating the need Funding information Paul I Terasaki Research FoundationMolecular mismatch load analysis was recently introduced as a means for performing risk stratification following organ transplantation. However, although good correlation was demonstrated between molecular mismatch load and generation of de novo donor-specific HLA antibody (DSA), quite a few exceptions exist, and the underlying factors that define HLA immunogenicity remain unclear. Herein, we present a new paradigm to interrogate differences between molecular mismatches that lead to the generation of de novo DSA and those that do not (the 2MM1DSA cohort).Specifically, patients transplanted across 2 HLA-DQ mismatches, who formed de novo DSA only to one mismatch (foe) but not the other (friend), provide a unique environment in which patient-specific factors that affect the immune response other than immunogenicity, such as infection and immunosuppression, can be controlled for. It further permits focusing on mismatches uniquely exhibited by the de novo DSA allele, rather than mismatches shared by both DSA and non-DSA alleles. This concept paper illustrates several examples, highlights the need for center-specific or population-specific cutoff values for posttransplant risk stratification, and mostly argues that if there is no direct correlation between molecular mismatch load and immunogenicity, then molecular mismatch load must not be adopted as an approach for equitable organ allocation. K E Y W O R D Salloantibody, antigen presentation/recognition, clinical research/practice, histocompatibility, organ allocation

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“…Broad antigen HLA-DQ matching between each recipient and donor on the basis of serologic typing is available for the majority of kidney transplant recipients in the United Network for Organ Sharing (UNOS) registry (15). Using UNOS data, we sought to determine the effect of HLA-DQ matching on acute rejection and graft loss after kidney transplantation.…”

Section: Introductionmentioning

confidence: 99%