How to select the best available related or unrelated donor of hematopoietic stem cells?

Tiercy, Jean‐Marie

doi:10.3324/haematol.2015.141119

Cited by 154 publications

(127 citation statements)

References 66 publications

(111 reference statements)

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“…The outcome of 63 MLR assays showed a large heterogeneity of the alloresponse with 52% positive tests. We first confirmed that MMs differing either outside the α1/α2 domains (C*02:02/02:29, α3 domain) or within the α1/α2 domains but not affecting peptide/TCR binding (C*03:03/03:04, residue 91 in the α2 domain) are not recognized by CD8 + alloreactive T cells and could therefore be considered as permissive MMs (28, 29). Next, we confirmed that the C*14:02 MM was able to induce a positive alloresponse in five of seven tested combinations, with two responses among the highest values (>10%) of CD137 + CD8 + T lymphocytes.…”

Section: Discussionsupporting

confidence: 57%

“…For patients with less common HLA haplotypes, 9/10-matched donors with a single HLA-C MM can represent the best option, but such incompatible transplants are characterized by increased risk of posttransplant complications (15, 16, 28). Some clinical studies have proposed that the alloresponse may vary with the nature of the HLA-C MM (12–14), although reliable prediction of less detrimental MMs remains a difficult task.…”

Section: Discussionmentioning

confidence: 99%

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Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

2016

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HLA-C locus mismatches (MMs) are the most frequent class I disparities in unrelated hematopoietic stem cell transplantation (HSCT) and have a detrimental impact on clinical outcome. Recently, a few retrospective clinical studies have reported some variability in the immunogenicity of HLA-C incompatibilities. To get better insight into presumably permissive HLA-C MMs, we have developed a one-way in vitro mixed lymphocyte reaction (MLR) assay allowing to quantify activated CD56−CD137+CD8+ lymphocytes in HLA-C incompatible combinations. T cell-mediated alloresponses were correlated with genetic markers such as HLA-C mRNA expression and the number of amino acid (aa) MMs in the α1/α2 domains (peptide-binding region). Because of the high rate of HLA-DPB1 incompatibilities in HLA-A-, B-, C-, DRB1-, and DQB1-matched unrelated HSCT patient/donor pairs, the impact of HLA-DPB1 mismatching, a potential bystander of CD4+ T cell activation, was also considered. Heterogeneous alloresponses were measured in 63 HLA-C-mismatched pairs with a positive assay in 52% of the combinations (2.3–18.6% activated CTLs), representing 24 different HLA-A~B~DRB1~DQB1 haplotypes. There was no correlation between measured alloresponses and mRNA expression of the mismatched HLA-C alleles. The HLA-C*03:03/03:04 MM did not induce any positive alloresponse in five MLRs. We also identified HLA-C*02:02 and HLA-C*06:02 as mismatched alleles with lower immunogenicity, and HLA-C*14:02 as a more immunogenic MM. A difference of at least 10 aa residues known to impact peptide/T cell receptor (TCR) binding and a bystander HLA-DPB1 incompatibility had a significant impact on CTL alloreactivity (p = 0.021). The same HLA-C MM, when recognized by two different responders with the same HLA haplotypes, was recognized differently, emphasizing the role of the T-cell repertoire of responding cells. In conclusion, mismatched HLA-C alleles differing by 10 or more aas in the peptide/TCR-binding region, when occurring together with HLA-DPB1 incompatibilities, should be considered as high-risk MMs in unrelated HSCT.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

2016

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“…HLA antigens are highly polymorphic and compatibility between donor and recipients of stem cell transplantation is essential for a successful outcome . The list of new HLA alleles continues to grow (http://www.ebi.ac.uk/ipd/imgt/hla).…”

Section: Conflict Of Interestmentioning

confidence: 99%

Identification of the novel HLA‐B08:01:01:02* allele in a Saudi individual

Alshubaili¹,

Alanazi²,

Alburaq³

et al. 2018

HLA

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“…В то же время появляются данные о вли-янии на выживаемость пациентов локусов HLA-DRB3 и HLA-DRB4. При этом не установлены различия в степени отрицательного влияния на отдаленные ре-зультаты алло-ТГСК между генной и аллельной несов-местимостью [14].…”

Section: *оригинальная лекция подготовлена по данным доклада предстunclassified

Selection of donor of allogeneic hematopoietic stem cell transplantation

Владимирович¹,

Зубаровская²,

Алянский³

et al. 2016

Ross. ž. det. gematol. onkol.

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How to select the best available related or unrelated donor of hematopoietic stem cells?

Abstract: This review article is based on an educational manuscript from the EHA20 meeting (Vienna, June 2015)

Cited by 154 publications

References 66 publications

Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

Identification of the novel HLA‐B08:01:01:02* allele in a Saudi individual

Selection of donor of allogeneic hematopoietic stem cell transplantation

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How to select the best available related or unrelated donor of hematopoietic stem cells?

Abstract: This review article is based on an educational manuscript from the EHA20 meeting (Vienna, June 2015)

Cited by 154 publications

References 66 publications

Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

Allorecognition of HLA-C Mismatches by CD8+ T Cells in Hematopoietic Stem Cell Transplantation Is a Complex Interplay between Mismatched Peptide-Binding Region Residues, HLA-C Expression, and HLA-DPB1 Disparities

Identification of the novel HLA‐B*08:01:01:02 allele in a Saudi individual

Selection of donor of allogeneic hematopoietic stem cell transplantation

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Identification of the novel HLA‐B08:01:01:02* allele in a Saudi individual