A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation

Zino, Elisabetta; Frumento, Guido; Marktel, Sarah; Sormani, Maria Pia; Ficara, Francesca; Terlizzi, Simona Di; Parodi, Alice; Sergeant, Ruhena; Martinetti, Miryam; Bontadini, Andrea; Bonifazi, Francesca; Lisini, Daniela; Mazzi, Benedetta; Rossini, Silvano; Servida, Paolo; Ciceri, Fabio; Bonini, Chiara; Lanino, Edoardo; Bandini, Giuseppe; Locatelli, Franco; Apperley, Jane F.; Bacigalupo, Andrea; Ferrara, Giovanni Battista; Bordignon, Claudio; Fleischhauer, Katharina

doi:10.1182/blood-2003-04-1279

Cited by 201 publications

(299 citation statements)

References 49 publications

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“…Disparities between HLA sequence polymorphisms detected by serology are termed antigen mismatches; those identified only by DNA-based typing are termed allele mismatches. The risk of mortality after unrelated HSCT transplants is increased by mismatches at a single allele at HLA -A -B -C -DRB1, DQB1 and recently at DPB1 (Zino et al, 2004). The significance of these mismatches must be taken into account prior to further analysis of the data for the role of non-HLA immunogenetics in the unrelated HSCT setting.…”

Section: Hla Associationmentioning

confidence: 99%

Genetic polymorphisms predicting the outcome of bone marrow transplants

et al. 2004

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SummaryAnalysis of non‐histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA‐matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor α, interleukin‐10, interferon γ and interleukin (IL)‐6, associate with more severe acute graft‐versus‐host disease (aGvHD). Donor genotype for IL‐1 receptor antagonist (IL‐1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL‐1Ra, IL‐6 and donor IL‐1α) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FCγ receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate‐reductase, have been associated with aGvHD and other post‐transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA‐matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non‐HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT.

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Section: Hla Associationmentioning

confidence: 99%

Genetic polymorphisms predicting the outcome of bone marrow transplants

et al. 2004

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“…Thereafter, Zino et al, published their T-cell epitope based HLA-DPB1 matching results. 13 In this study, the presence of nonpermissive HLA-DPB1 mismatches was correlated with an increased risk of grade II-IV aGVHD and transplantation-related mortality (TRM) but not relapse, as compared with the permissive group. There was also a marked but statistically unsignificant decrease in OS.…”

Section: Discussionmentioning

confidence: 94%

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in the study by Loiseau et al reported increased frequency of severe aGVHD and poorer survival in two HLA-DP incompatibilities in a group of unrelated ASCT patients. 10 In this study they were not able show a significant relationship between HLA-DP mismatches and disease relapse.…”

Section: Discussionmentioning

confidence: 99%

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

Kantarcıoğlu¹

2017

UHOD

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In this study, we retrospectively examined 34 donor/recipient transplant pairs fully tested for the alleles HLA-A, B, C, DRB1, DQB1 and DPB1 in two different centers in Istanbul, Turkey. HLA-DPB1 disparity in at least one antigen level was 79.6% and only 20.6% of transplant pairs were fully identical for HLA-DPB1, in our study group. Neutrophil and thrombocyte engraftment successfully occurred in the entire study group. When the occurrence of severe (Grade III-IV) aGVHD was taken into account, we have observed that, non-permissive HLA-DPB1 mismatches were a significant factor for development of severe aGVHD (p= 0.019). There was a trend of increasing significance for the gut (p= 0.006) and liver (p: 0.054) aGVHD but not for skin aGVHD in non-permissive HLA-DPB1 mismatched transplantations. In multivariate analysis, non-permissive HLA-DPB1 mismatches remained as an independent factor for severe aGVHD. Our results did not show a significant impact of HLA-DPB1 mismatches on relapse. In survival analysis, both HLA-DPB1 disparities and non-permissive mismatches showed a decreasing trend of event free and overall survival times. Considering these results during donor selection may improve transplant outcomes in the setting of unrelated ASCT.

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“…7,8 An algorithm for the determination of non-permissive HLA-DPB1 disparities, which were found to be associated with a significantly increased risk of TRM and grades II-IV acute GvHD, in patients transplanted for malignant hematopoietic disorders, has been recently proposed. 15 This algorithm, based on the identification of an immunogenic T-cell epitope shared by a defined subset of HLA-DBP1 alleles, which, if expressed by self-HLA-DP molecules protects from mounting a response against allogeneic HLA-DP antigens carrying the epitope, 15,16 proved also to predict the occurrence of graft failure in children with thalassemia major transplanted with BM cells from an unrelated volunteer. 17 Thus, at least in some groups of patients transplanted from an unrelated volunteer, the incidence of immune complications (namely GvHD and graft failure) can be reduced by appropriate selection of the donor, taking into account the functional rules of immune genetics.…”

Section: Unrelated Bm Donorsmentioning

confidence: 99%

Searching for alternative hematopoietic stem cell donors for pediatric patients

Rocha

Locatelli

2007

Bone Marrow Transplant

148

110

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The use of alternative hematopoietic stem cell (HSC) donors has been witnessing important progress, mainly due to: (i) better HLA matching at the allelic level between donor and recipient in unrelated HSC transplantation (HSCT) translating into better patient outcome; (ii) better donor choice and patient selection in unrelated, often HLA-mismatched, cord blood transplantation and (iii) new strategies of adoptive cell therapy aimed at improving the results of T-cell-depleted haploidentical HSCT from a relative. Currently, it is possible to find an HSC donor for virtually almost all children with an indication to receive allogeneic HSCT and lacking an HLA-identical sibling. Each of the three options of HSCT from alternative donors has advantages and limitations. Therefore, any physician has to carefully evaluate, for each single pediatric patient in need of an allograft, all the possible alternatives to choose the best HSC donor, taking into account type of disease to be treated, urgency of transplantation, donor characteristics and center's experience. This review will analyze in detail the advantages and limitations of each of the three options of alternative donor HSCT and the main criteria to be used for choosing the most suitable donor for pediatric patients lacking an HLA-identical sibling.

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A T-cell epitope encoded by a subset of HLA-DPB1 alleles determines nonpermissive mismatches for hematologic stem cell transplantation

Cited by 201 publications

References 49 publications

Genetic polymorphisms predicting the outcome of bone marrow transplants

Genetic polymorphisms predicting the outcome of bone marrow transplants

Impact of HLA-DPB1 Matching in Unrelated Allogeneic Stem Cell Transplantation: Results of Two Centers From Turkey

Searching for alternative hematopoietic stem cell donors for pediatric patients

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