World Marrow Donor Association guidelines for the reporting of novel <scp>HLA</scp> alleles

Hofmann, Jan A.; Bochtler, Werner; Robinson, James T.; Sauter, Jürgen; Askar, Medhat; Houdová, Lucie; Melchers, Mark; Schmidt, Alexander H.; Spierings, Eric; Urban, Christine; Venter, Alicia; Maiers, Martin; Marsh, S. G. E.; Eberhard, Hans-Peter

doi:10.1111/tan.15048

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…In the absence of an HLA-identical donor, umbilical cord blood (UCB) is an alternative cell source for haematopoietic cell transplantation (HCT). Minimum HLA requirements for an unrelated donor search have been established [1][2][3][4] ; however, due to the naive characteristics of UCB immune cells, in the setting of UCBT, these requirements are less stringent. 5,6 Nevertheless, the degree of HLA mismatch clearly affects outcomes after UCBT.…”

Section: Introductionmentioning

confidence: 99%

HLA peptide‐binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia

Boukouaci,

Rivera‐Franco,

Volt

et al. 2024

Br J Haematol

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SummaryPocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft‐versus‐host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA‐C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA‐A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA‐C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA‐DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA‐B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA‐DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA‐A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA‐C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA‐mediated cellular interactions and their role in the development of GVHD and relapse.

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Section: Introductionmentioning

confidence: 99%

HLA peptide‐binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia

Boukouaci,

Rivera‐Franco,

Volt

et al. 2024

Br J Haematol

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Novel alleles in the era of next-generation sequencing-based HLA typing calls for standardization and policy

Tran,

Sherwood,

Mostafa

et al. 2023

Front. Genet.

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Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed. Here, we describe the experience of a clinical histocompatibility laboratory’s use of NGS for HLA genotyping and its management of novel alleles detected in an ethnically-diverse population of British Columbia, Canada. Over a period of 18 months, 3,450 clinical samples collected for the purpose of solid organ or hematopoietic stem cell transplantation were sequenced using NGS. Overall, 29 unique novel alleles were identified at a rate of ∼1.6 per month. The majority of novelties (52%) were detected in the alpha chains of class II (HLA-DQA1 and -DPA1). Novelties were found in all 11 HLA classical genes except for HLA-DRB3, -DRB4, and -DQB1. All novelties were single nucleotide polymorphisms, where more than half led to an amino acid change, and one resulted in a premature stop codon. Missense mutations were evaluated for changes in their amino acid properties to assess the potential effect on the novel HLA protein. All novelties identified were confirmed independently at another accredited HLA laboratory using a different NGS assay and platform to ensure validity in the reporting of novelties. The novel alleles were submitted to the Immuno Polymorphism Database-Immunogenetics/HLA (IPD-IMGT/HLA) for official allele name designation and inclusion in future database releases. A nationwide survey involving all Canadian HLA laboratories confirmed the common occurrence of novel allele detection but identified a wide variability in the assessment and reporting of novelties. In summary, a considerable proportion of novel alleles were identified in routine clinical testing. We propose a framework for the standardization of policies on the clinical management of novel alleles and inclusion in proficiency testing programs in the era of NGS-based HLA genotyping.

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World Marrow Donor Association guidelines for the reporting of novel HLA alleles

Cited by 2 publications

References 12 publications

HLA peptide‐binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia

HLA peptide‐binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia

Novel alleles in the era of next-generation sequencing-based HLA typing calls for standardization and policy

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