HLA‐A*24020102L in the UK blood donor population

Dunn, P. P. J.; Turton, JP; Downing, Jonathan; Williams, S.; Navarrete, Cristina; Darke, C.

doi:10.1111/j.0001-2815.2004.00233.x

Cited by 6 publications

(7 citation statements)

References 14 publications

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“…HLA‐A*32:11Q has originally been classified as ‘Q’ allele because its surface expression was not known. Three reasons for this condition have been proposed so far: (i) reduced mRNA transcription, (ii) decreased stability of mRNA transcripts and (iii) alterations in secondary structures of the HLA heavy chains (25–30). Here, we found no differences between HLA‐A*32:01 and HLA‐A*32:11Q in terms of mRNA levels.…”

Section: Discussionsupporting

confidence: 45%

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

et al. 2012

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Matching of human leukocyte antigen (HLA) alleles between donors and recipients plays a major role in hematopoietic stem cell transplantation (HSCT). Null or questionably expressed HLA allelic variants are a major issue in HLA matching, because the aberrant expression of such alleles can have a major impact on the outcome of HSCT and/or its complications such as graft-versus-host disease. The goal of this study was to investigate the potential of a recently developed cytokine-induced secretion assay to differentiate the expression levels of HLA-A*32:11Q (questionable) into a null (N) or low (L) expression variant. An amino acid mutation at position 164 of HLA-A*32:11Q disrupts the disulfide bridge in the α2 domain. HLA-A*32:11Q is not detectable by standard microlymphocytotoxicity assay. To this end, we cloned soluble HLA-A*32:11Q and a reference allele (HLA-A*32:01) into expression vectors and transfected/transduced HEK293 and K562 cells. Allele-expressing K562 cells were simultaneously transfected/transduced with a β2-microglobulin (B2M)-encoding vector to ensure the intact HLA structure with B2M. After treatment with proinflammatory cytokines, secreted soluble HLA molecules were determined by enzyme-linked immunosorbent assay in the supernatant and intracellular accumulation of the recombinant proteins by flow cytometry. HLA-A*32:11Q was nearly undetectable in untreated transfectants. Cytokine treatment increased the secretion of HLA-A*32:11Q to detectable levels and resulted in intracellular accumulation of the allele. There was no difference in mRNA transcription between the A*32 alleles. On the basis of these results, we recommend reclassification of HLA-A*32:11Q as a low expression (L) variant.

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Section: Discussionsupporting

confidence: 45%

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

et al. 2012

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“…There have been several reports on HLA expression variants, for example, the expression of HLA‐A*24:02:01:02L was affected by alternative splicing, and the silencing of HLA‐A*01:11N expression was attributed to the introduction of a new splice site that caused the deletion of nucleotides . The results of our study suggested that a mutation in C*07:02:01:17N disrupted an initial splice site, resulting in the expression of an aberrant form of the original allele, C*07:02:01:01 .…”

Section: Hla‐c*07:02:01:17n (Ddbj #Lc314771)mentioning

confidence: 54%

A novel HLA‐C allele, HLA‐C07:02:01:17N*, with an alternative splice site

Shimizu

Kuroda

Nakajima

et al. 2018

HLA

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“…In case number 3, the patient with the A*24020102L allele was of Iranian descent. The common haplotype associated with this allele in the British population and in a Czech patient is A*24020102L, B55, Cw01 (7, 8). In this case, it was found in the haplotype HLA‐A*24020102L, HLA‐B*1801, HLA‐Cw*(0401 or 0701/06).…”

Section: Discussionmentioning

confidence: 99%

HLA class I null alleles and new alleles affect unrelated bone marrow donor searches

et al. 2005

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Unrecognized HLA null alleles or new alleles may affect the outcome of bone marrow transplants using unrelated donors. Some reports suggest that null alleles occur in the range of 0.003-0.07% (1, 2), which has led some transplant programs to stop performing serologic typing. We describe nine cases involving expression variants or new alleles. Three cases involved expression variants, including two null alleles and A*24020102L. One of the null alleles was a new variant of A*02. Seven cases involved new alleles. In five cases, there where discrepancies between HLA typing by serology and PCR-SSP. These included the three expression variants, one new B40 allele that typed serologically as B41 and one new B*07 allele that typed serologically as B42. Eight of these cases were found in the course of typing bone marrow transplant patients or potential unrelated donors since May of 2001 (total tested, 710 patients, 1914 donors). Thus, the incidence of null alleles was two in 2,624 (0.08%). Sequence-based typing (SBT) was performed on 676 of these samples. The decision to perform SBT was influenced by finding a serologic typing discrepancy in two cases. In one of those cases, SBT would probably have been performed at a later time, prior to final selection of a donor. Thus, the incidence of new alleles was between 4 and 6 of 676 (0.59-0.89%). We conclude that new HLA alleles and null alleles are uncommon but not extremely rare, and they continue to affect a significant number of unrelated donor searches.

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HLA‐A*24020102L in the UK blood donor population

Cited by 6 publications

References 14 publications

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

A novel HLA‐C allele, HLA‐C07:02:01:17N*, with an alternative splice site

HLA class I null alleles and new alleles affect unrelated bone marrow donor searches

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HLA‐A*24020102L in the UK blood donor population

Cited by 6 publications

References 14 publications

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine‐induced secretion approach using HLA‐A*32:11Q

A novel HLA‐C allele, HLA‐C*07:02:01:17N, with an alternative splice site

HLA class I null alleles and new alleles affect unrelated bone marrow donor searches

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Product

Resources

About

A novel HLA‐C allele, HLA‐C07:02:01:17N*, with an alternative splice site