Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation

Lobashevsky, Andrew L.; Goggins, William C.; Rosner, Kevin M.; Taber, Tim E.

doi:10.1016/j.trim.2017.06.001

Cited by 6 publications

(10 citation statements)

References 51 publications

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“…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.…”

Section: Kubal Et Almentioning

confidence: 99%

“…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%

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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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Section: Kubal Et Almentioning

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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“…Similarly, studies evaluating the impact of DSA in FCXM-negative patients used different induction agents and desensitization protocols. 11,12,20,21 The aim of this study was to assess the effects of DSA strength and specificity on clinical outcomes in KT recipients positive on Luminex assays but negative on FCXM. To analyze the effect of DSA alone, patients who underwent desensitization prior to KT were excluded and only those administered anti-IL-2 receptor antibody (basiliximab) as an induction agent was included.…”

Section: Impact Of Pretransplant Donor-specific Antibodies On Kidney mentioning

confidence: 99%

“…The lack of consensus among these studies is due, at least in part, to the heterogeneity of induction regimens, desensitization protocols, and FCXM results. Similarly, studies evaluating the impact of DSA in FCXM‐negative patients used different induction agents and desensitization protocols …”

Section: Introductionmentioning

confidence: 99%

Impact of pretransplant donor‐specific antibodies on kidney allograft recipients with negative flow cytometry cross‐matches

Kwon

Kim

Choi

et al. 2018

Clinical Transplantation

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The Luminex test can detect low levels of donor-specific antibody (DSA) that cannot be detected by flow-cytometric cross-matching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA-negative and 81 (14.1%) were DSA-positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the 2 groups (P = .54), the incidence of antibody-mediated rejection (ABMR) was significantly higher in the DSA-positive group (P < .01). There was no statistically significant association between rejection-free graft survival (RFGS) rates and pretransplant class I DSA. However, evaluation of pretransplant class II DSA showed that RFGS rates were significantly lower in patients with mean fluorescence intensity (MFI) >3000 than in patients with DSA-negative (P < .01). On multivariate analyses, class II DSA MFI ≥5000 was a significant risk factor for acute rejection (hazard ratio, 7.48; P < .01). These findings suggested that pretransplant DSA alone did not affect graft survival in KT recipients without desensitization. However, class II DSA MFI >5000 was an independent predictor of acute rejection in DSA-positive patients.

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“…In this study, the 127K epitope was found to be immunogenic, and when unmatched at this epitope, they observed an odds ratio of 9 for a deleterious effect. They detected a threshold of 12 eplets for MM, with anything higher than this being a strong predictor of a poor outcome [24]. However, to better define the role of eplet MM load in alloresponse, a profound definition of eplet immunogenicity should be provided [40].…”

Section: Renalmentioning

confidence: 99%

Epitope-Level Matching—A Review of the Novel Concept of Eplets in Transplant Histocompatibility

Renaldo¹,

Roa-Bautista²,

González-López³

et al. 2021

Transplantology

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The development of de novo donor-specific antibodies is related to the poor matching of the human leukocyte antigen (HLA) between donor and recipient, which leads to dismal clinical outcomes and graft loss. However, new approaches that stratify the risks of long-term graft failure in solid organ transplantation have emerged, changing the paradigm of HLA compatibility. In addition, advances in software development have given rise to a new structurally based algorithm known as HLA Matchmaker, which determines compatibility at the epitope rather than the antigen level. Although this technique still has limitations, plenty of research maintains that this assessment represents a more complete and detailed definition of HLA compatibility. This review summarizes recent aspects of eplet mismatches, highlighting the most recent advances and future research directions.

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Immunogenicity of Class I HLA but not preformed low MFI donor specific antibodies correlates with outcomes after first renal transplantation

Cited by 6 publications

References 51 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

Impact of pretransplant donor‐specific antibodies on kidney allograft recipients with negative flow cytometry cross‐matches

Epitope-Level Matching—A Review of the Novel Concept of Eplets in Transplant Histocompatibility

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