HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients

Sullivan, Patrick M.; Warner, Paul; Kemna, Mariska; Albers, E.; Law, Sabrina; Weiss, Noel S.; Law, Yuk M.

doi:10.1016/j.healun.2014.12.017

Cited by 40 publications

(29 citation statements)

References 21 publications

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“…The recent advances based on an understanding of molecular models of HLA epitope structures and their reactivity with antibodies have led to donor‐recipient matching at the epitope level instead of by HLAs. Epitope‐based matching has already shown improvement of outcomes in other organs . Some studies have shown that HLA class I and class II MMs with low eplet loads are less likely to induce antibody responses .…”

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confidence: 99%

“…Epitope-based matching has already shown improvement of outcomes in other organs. (9)(10)(11)(12)(13)(14) Some studies have shown that HLA class I and class II MMs with low eplet loads are less likely to induce antibody responses. (15) Recently, Willicombe et al demonstrated that the epitope MM burden predicts the risk of dn-DSA formation in kidney transplantation.…”

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confidence: 99%

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Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

et al. 2018

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Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with longterm immunologic complications after liver transplantation (LT). We hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT recipients were prospectively screened for dn-DSA by a Luminex single-antigen test (One Lambda, Inc., Canoga Park, CA) at 1, 2, 3, 6, 12, 18, 24, and 36 months after LT. HLA typing of the recipients and donors was performed using polymerase chain reaction (PCR)-SSP and PCR-SSOP Luminex low-resolution methods (One Lambda, Inc.). The HLAMatchmaker computer algorithm was used for identification of MM eplets at HLA-DRB1 and -DQA1/B1 loci. Luminex single-antigen bead solid phase assay was used for antibody analysis. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus maintenance. There were 27 (34%) patients who developed dn-DSA. There were no episodes of antibody-mediated rejection, and 9 (11%) developed acute cellular rejection (ACR). A positive crossmatch status and a higher number of HLA-A, -B, -DR, and -ABDR MMs were not associated with dn-DSA formation. Patients developing dn-DSA had a significantly higher number of total (38 ± 2.7 versus 28 ± 2.3; P = 0.01) and antibody-verified (AbVer; 14 ± 1.1 versus 10 ± 1; P = 0.015) class II MM eplets. By a multivariate regression analysis, the number of class II MM eplets was strongly associated with risk of class II dn-DSA formation (odds ratio [OR], 1.2; P < 0.01). Patients with ACR had a significantly higher number of total (20.2 ± 1.3 versus 13.9 ± 0.9; P < 0.01) as well as AbVer (10.7 ± 1.1 versus 7.5 ± 0.6; P = 0.03) class I MM eplets. In conclusion, donor-recipient HLA epitope MM is associated with a risk of dn-DSA formation and rejection after LT. However, further studies are required to evaluate the clinical utility of epitope matching in LT.

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confidence: 99%

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confidence: 99%

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

et al. 2018

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“…Patients who were transplanted with a higher number of mismatched eplets have a higher risk for donor-specific HLA antibody formation after transplantation (Daniels et al 2018;Duquesnoy et al 2008a;Kubal et al 2018;McCaughan et al 2018;Walton et al 2018;Wiebe et al 2013). Moreover, additional studies suggest that matching based on the number of eplets may lead to an improved graft outcome in kidney (Wiebe et al 2013), heart (Sullivan et al 2015), lung (Walton et al 2016), liver (Ekong et al 2019), and cornea transplantation (Bohringer et al 2010).…”

Section: Introductionmentioning

confidence: 99%

PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation

Geneugelijk

Spierings

2019

Immunogenetics

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Human leukocyte antigen (HLA) mismatches between donors and recipients may lead to alloreactivity after solid organ transplantation. Over the last few decades, our knowledge of the complexity of the HLA system has dramatically increased, as numerous new HLA alleles have been identified. As a result, the likelihood of alloreactive responses towards HLA mismatches after solid organ transplantation cannot easily be assessed. Algorithms are promising solutions to estimate the risk for alloreactivity after solid organ transplantation. In this review, we show that the recently developed PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) algorithm can be used to minimize alloreactivity towards HLA mismatches. Together with the use of other algorithms and simulation approaches, the PIRCHE-II algorithm aims for a better estimated alloreactive risk for individual patients and eventually an improved graft survival after solid organ transplantation.

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“…Eplet MMs in kidney transplantation have been demonstrated as a more accurate determinant of the risk of HLA antibody development for both class I and class II and have also been implemented in a successful program to facilitate identification of acceptable mismatched donors for highly sensitized patients in Europe, the Eurotransplant Acceptable Mismatch Program . Reports of the use of HLAMatchmaker cases in the pediatric transplant literature are limited …”

Section: Introductionmentioning

confidence: 99%

“…24 Reports of the use of HLAMatchmaker cases in the pediatric transplant literature are limited. 25,26 In 2011, the Transplantation Society of Australia and New Zealand (TSANZ) introduced a points bonus in the national allocation algorithm for any child under 18 years, who had been on dialysis for >12 months and progressively introduced this system in states across the country. 27 In order to maximize the benefits of this bonus for children transplanted at the Royal Children's Hospital Melbourne (RCH), a program was developed using HLA eplet matching criteria to minimize the possibility of transplanting kidneys likely to result in broad sensitization, while simultaneously achieve timely access to transplantation.…”

Section: Introductionmentioning

confidence: 99%

Application of an epitope‐based allocation system in pediatric kidney transplantation

Kausman

Walker

Cantwell

et al. 2016

Pediatric Transplantation

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Donor-recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope-based allocation approach to prospectively exclude donors with high-level mismatches was implemented for pediatric KTRs on the DD waiting list. Nineteen consecutive transplants were followed for 12 months, including eight DD KTRs listed with eplet exclusions, as well as three DD KTRs and eight LD KTRs without exclusions. KTRs with eplet exclusions had estimated GFR of 78.5 mL/min/1.73 m , no episodes of rejection, and time to transplant 6.55 months. HLA-A, HLA-B, HLA-DR antigen mismatches were similar between all groups. KTRs with exclusions had significantly lower class II eplet mismatches (20.4) than the contemporary DD KTRs without exclusions (63.7) and DD KTRs transplanted in the preceding decade (46.9). dnDSAs were identified in two of eight DD KTRs with exclusions, two of three DD KTRs without exclusions and five of eight LD KTRs. Epitope-based allocation achieved timely access to transplantation, low class II eplet mismatches, and low rates of dnDSAs in the first year. This strategy requires longer follow-up and larger numbers, but has the potential to reduce anti-HLA sensitization and improve both graft survival and opportunities for future retransplantation.

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HLA molecular epitope mismatching and long-term graft loss in pediatric heart transplant recipients

Cited by 40 publications

References 21 publications

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation

Application of an epitope‐based allocation system in pediatric kidney transplantation

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