The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT

Pasi, Annamaria; Crocchiolo, Roberto; Bontempelli, Mario; Carcassi, Carlo; Carella, Graziella; Crespiatico, L.; Garbarino, Lucia; Mascaretti, L; Mazzi, Benedetta; Mazzola, Gina; Miotti, Valeria; Porfirio, Berardino; Tagliaferri, C.; Valentini, Tiziana; Vecchiato, Cinzia; Fleischhauer, Katharina; Sacchi, Nicoletta; Bosi, Alberto; Martinetti, Miryam

doi:10.1038/bmt.2010.246

Cited by 25 publications

(16 citation statements)

References 27 publications

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“…Of the 35 DRB1 mismatches, 4 only were accompanied by a DRB3 mismatch, with 2 of these including a DRB1*14:01/14:54 mismatch previously reported as permissive. 29 Interestingly, 22% of the DQB1 incompatibilities consisted of the DQB1*03:01/03:02 mismatch that had been shown to be undetectable in mixed lymphocyte Table 2. Abbreviations: aGvHD = acute graft versus host disease; cGvHD = chronic graft versus host disease; GVHD = graft-versus-host disease; TRM = transplant-related mortality.…”

Section: Discussionmentioning

confidence: 99%

High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities

Passweg

Schanz

Chalandon

et al. 2015

Bone Marrow Transplant

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Unrelated donor searches in Switzerland require high-resolution HLA typing for HLA-A/B/C/DRB1/DRB3,4/DQB1 loci. We evaluated this strategy accepting donors with ⩾ 9/10 match. Of 802 unrelated donor transplants in 2000-2013, 570 were 10/10 matched, 31 were DRB3/4 mismatched, 261 were single-allele mismatched and 13 had 2 allele mismatches. Of the 261 single-allele disparities, 60 concerned HLA-A/-B, 55 HLA-C and 73 HLA-DRB1/-DQB1 loci. Transplants were reduced intensity conditioning (289, 36%), marrow (187, 23%), EBMT risk score was low in 39, intermediate I in 331, intermediate II in 333 and high in 99 patients. Five-year survival was 48 ± 4%. HLA affected survival in the multivariate model adjusted for risk score. HLA-A/-B and HLA-C mismatches had twice the mortality risks, whereas HLA-DRB1/-DQB1 mismatches were similar to matched transplants. HLA-DRB3/4 mismatches were associated with a nonsignificant increased mortality risk. HLA-DRB3/4 mismatches had higher graft-versus-host disease and transplant-related mortality risks and lower relapse rates compared with matched transplants. We show significant effects of HLA class I, but not HLA class II, mismatches. The lack of impact of DRB1 disparities may be related to the lower immunogenicity of the DRB1*11:01/11:04 and DRB1*14:01/14:54 mismatches, representing 46% of DRB1 incompatibilities. These results support a matching algorithm that prioritizes mismatches considered as more permissive.

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Section: Discussionmentioning

confidence: 99%

High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities

Passweg

Schanz

Chalandon

et al. 2015

Bone Marrow Transplant

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“…HLA high-resolution match is defined as equivalent amino acid sequences (G group) in the antigen recognition site (ARS; exon 2 and 3 for HLA Class I and exon 2 for HLA Class II) of the molecule that binds peptide and interacts with the T cell receptor [11]. The impact of variation outside the ARS is not well characterized because of limitations of the current typing methodologies and a lack of clinical correlation studies [12-13]. …”

Section: Unrelated Donor Stem Cell Transplantsmentioning

confidence: 99%

Recommendations for Donor Human Leukocyte Antigen Assessment and Matching for Allogeneic Stem Cell Transplantation: Consensus Opinion of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

Howard¹,

Fernández-Viña

Appelbaum

et al. 2015

Biology of Blood and Marrow Transplantation

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The Blood and Marrow Transplant Clinical Trials Network conducts large, multi-institutional clinical trials with the goal of improving the outcomes of hematopoietic cell transplantation (HCT) for patients with life-threatening disorders. Well designed HCT trials benefit from standardized criteria for defining diagnoses, treatment plans and graft source selection. In this perspective, we summarize evidence supporting criteria for the selection of related and unrelated adult volunteer progenitor cell donors or umbilical cord blood units. These standardized criteria for graft source selection have been adopted by the BMT CTN to enhance the interpretation of clinical findings within and among future clinical protocols.

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“…This study also showed that four of six samples previously typed as HLA‐DRB1*14:01 appeared to be HLA‐DRB1*14:54 . Also in other studies, it has been shown that DRB1*14:54 is more frequent than DRB1*14:01 . Therefore, the Common and Well Documented (CWD) database listed the HLA‐DRB1*14:54 allele as common, indicating that high resolution typing of all exons is required for an appropriate CWD allele definition .…”

Section: Introductionmentioning

confidence: 52%

Full‐length HLA‐DRB1 coding sequences generated by a hemizygous RNA‐SBT approach

et al. 2015

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Currently 1582 HLA-DRB1 alleles have been identified in the IMGT/HLA database (v3.18). Among those alleles, more than 90% have incomplete allele sequences, which complicates the analysis of the functional relevance of polymorphism beyond exon 2. The polymorphic index of each individual exon of the currently known allele sequences, shows that polymorphism is present in all exons, albeit not equally abundant. Full-length HLA-DRB1 RNA sequencing identifies polymorphism of the complete coding region. Here we describe a hemizygous full-length RNA sequence-based typing (SBT) approach based on group-specific HLA-DRB1 amplification and subsequent sequencing. RNA full-length sequences can easily be accessed because of the short amplicon length (801 bp). The RNA-SBT approach was successfully validated on a panel of DRB1 alleles having fully known coding sequences according to the IMGT/HLA database, and cover all serological equivalents. Subsequently, the approach was applied on a panel of 54 alleles with incomplete allele sequences, resulting in full-length coding sequences and the identification of one new and one corrected allele. This study shows the universal applicability of the RNA-based sequencing approach to identify full-length coding sequences and to define the polymorphic content of HLA-DRB1 alleles.

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The conundrum of HLA-DRB114:01/14:54 and HLA-DRB302:01/02:02 mismatches in unrelated hematopoietic SCT

Cited by 25 publications

References 27 publications

High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities

High-resolution HLA matching in unrelated donor transplantation in Switzerland: differential impact of class I and class II mismatches may reflect selection of nonimmunogenic or weakly immunogenic DRB1/DQB1 disparities

Recommendations for Donor Human Leukocyte Antigen Assessment and Matching for Allogeneic Stem Cell Transplantation: Consensus Opinion of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

Full‐length HLA‐DRB1 coding sequences generated by a hemizygous RNA‐SBT approach

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