HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction

Walton, D.C.; Hiho, Steven; Cantwell, Linda; Diviney, Mary; Wright, S.; Snell, Gregory I; Paraskeva, Miranda; Westall, Glen P.

doi:10.1111/ajt.13798

Cited by 72 publications

(56 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with evidence from transplantation of other solid organs, recent studies indicate that total HLA mismatches are associated with an increased risk for CLAD (54, 62). Hayes et al described an increased risk for BOS, with HLA-A mismatches being associated with a greater hazard (54), whereas Walton et al demonstrated the importance of eplet mismatches as a risk factor for RAS (62).…”

Section: Discussionmentioning

confidence: 59%

See 1 more Smart Citation

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Koutsokera¹,

Royer²,

Antonietti³

et al. 2017

Front. Med.

View full text Add to dashboard Cite

BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

show abstract

Section: Discussionmentioning

confidence: 59%

“…Hayes et al described an increased risk for BOS, with HLA-A mismatches being associated with a greater hazard (54), whereas Walton et al demonstrated the importance of eplet mismatches as a risk factor for RAS (62). In our study, HLA mismatches were an independent risk factor of mortality in the multivariate model but not for BOS or RAS.…”

Section: Discussionmentioning

confidence: 99%

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Koutsokera¹,

Royer²,

Antonietti³

et al. 2017

Front. Med.

View full text Add to dashboard Cite

show abstract

“…For example, Duquesnoy reported on HLA epitope-based matching for organ transplantation [35, 36]. Wiebe reported on epitope matching to minimize de novo donor-specific antibodies to improve transplantation outcome [37] and Walton et al reported on the usefulness of matching at the epitope level which protects against chronic lung allograft dysfunction [38]. …”

Section: Discussionmentioning

confidence: 99%

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

El‐Awar

Jucaud

Nguyen

2017

Journal of Immunology Research

View full text Add to dashboard Cite

Sensitization to human leukocyte antigens (HLA) in organ transplant patients causes graft rejection, according to the humoral theory of transplantation. Sensitization is almost ubiquitous as anti-HLA antibodies are found in almost all sera of transplant recipients. Advances in testing assays and amino acid sequencing of HLA along with computer software contributed further to the understanding of antibody-antigen reactivity. It is commonly understood that antibodies bind to HLA antigens. With current knowledge of epitopes, it is more accurate to describe that antibodies bind to their target epitopes on the surface of HLA molecular chains. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of cross-reactivity in HLA testing, often explained as cross-reactive groups (CREGs) of antigens with antibody, can be clearly explained now by public epitopes. Since 2006, we defined and reported 194 HLA class I unique epitopes, including 56 cryptic epitopes on dissociated HLA class I heavy chains, 83 HLA class II epitopes, 60 epitopes on HLA-DRB1, 15 epitopes on HLA-DQB1, 3 epitopes on HLA-DQA1, 5 epitopes on HLA-DPB1, and 7 MICA epitopes. In this paper, we provide a summary of our findings.

show abstract

“…12,13 The eplet, however, is only one small part of the antigen surface that interacts with the antibody. A greater number of HLA eplet mismatches with the donor has been associated with an increased risk of dnDSA development.…”

Section: Introductionmentioning

confidence: 99%

Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation

McCaughan

Battle

Singh

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

The development of de novo donor-specific HLA antibodies (dnDSA) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dnDSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dnDSA development and to propose primary prevention strategies that could reduce the incidence of dnDSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265). HLA typing was performed and HLA antibody testing was undertaken before and after transplantation. HLAMatchmaker analysis was performed for persistent dnDSA to identify potentially more immunogenic eplet differences. Validation was performed in recipients of lung transplants from 2008 to 2013 (n = 433). The majority of recipients with dnDSA had antibodies to identical eplet positions on DQ2 and DQ7. A high-risk epitope mismatch (found in DQA1*05 + DQB1*02/DQB1*03:01(7)) was associated with a 4.2- and 4.9-fold increased risk of dnDSA in heart and lung recipients respectively. HLA electrostatic potential modeling provided a plausible explanation for this observed immunogenicity. A theoretical allocation algorithm avoiding high-risk epitope mismatches was generated and predicted to reduce dnDSA by up to 72% without additional testing, eplet analysis, or cost.

show abstract

HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction

Cited by 72 publications

References 26 publications

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

HLA Epitopes: The Targets of Monoclonal and Alloantibodies Defined

Identification of risk epitope mismatches associated with de novo donor-specific HLA antibody development in cardiothoracic transplantation

Contact Info

Product

Resources

About