Frequency of HLA-DPB1 disparities detected by reference strand-mediated conformation analysis in HLA-A, -B, and -DRB1 matched siblings

Büchler, Tomáš; Gallardo, David; Rodríguez-Luaces, Marta; Pujal, Josep-Maria; Grañena, A

doi:10.1016/s0198-8859(01)00376-7

Cited by 24 publications

(14 citation statements)

References 17 publications

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“…To the authors' knowledge, this is the most complex and polymorphic group of loci for which the utility of RSCA has been shown. Previous use of RSCA in humans and sheep has been restricted to amplicons containing up to two distinct alleles, in part as a result of the availability of locus‐specific PCR primers (11–13, 15, 17).…”

Section: Discussionmentioning

confidence: 99%

Resolution of complex feline leukocyte antigen DRB loci by reference strand‐mediated conformational analysis (RSCA)

et al. 2003

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The DRB genes of the domestic cat are highly polymorphic. Studies based on clonal sequence analysis have suggested the existence of two distinct loci within individual animals and good evidence for 24 distinct FLA-DRB alleles. This variability, the complexity of clonal sequence analysis and its susceptibility to PCR-induced artefacts has represented a bottleneck to further progress. In this study we have applied reference strand-mediated conformational analysis (RSCA) to FLA-DRB. This protocol has been shown to be highly reproducible. Using five reference strands including two derived from non-domestic felines, we could distinguish 23 FLA-DRB alleles. We used RSCA to explore genetic polymorphism of FLA-DRB in 71 cats including 31 for which clonal sequence analysis was also available. On average, RSCA identified 0.9 more alleles within cats than clonal sequence analysis. Reference strand-mediated conformational analysis was also able to identify animals containing new alleles that could be targeted for sequence analysis. Analysis of allele patterns showed clear evidence for different allele distributions between breeds of cats, and suggested the Burmese breed may have highly restricted FLA-DRB polymorphism. Results from two families provided clear evidence for variation in the number of DRB genes on different haplotypes, with some haplotypes carrying two genes and some containing three. This study highlights the utility of RSCA for the resolution of complex amplicons containing up to six distinct alleles. A simple, rapid method for characterizing FLA-DRB makes possible studies on vaccine response and susceptibility/resistance to viral infections, which are a significant clinical problem in cats.

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Section: Discussionmentioning

confidence: 99%

Resolution of complex feline leukocyte antigen DRB loci by reference strand‐mediated conformational analysis (RSCA)

et al. 2003

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“…Recombination hotspots are located between HLA‐DQB1 and ‐DPB1 genes (Cullen et al ., ); therefore, matching patients and unrelated donors with common HLA‐A, ‐C, ‐B, ‐DRB1, ‐DQB1 haplotypes does not necessarily implicate matching for HLA‐DPB1 and ‐DPA1 alleles. It is reported that within families up to 5% of otherwise 10/10 matched siblings will also be HLA‐DPB1 mismatched attributed to recombination between HLA‐DQ and ‐DP genes (Büchler et al ., ). HLA‐DP‐specific T cells have been detected and associated with both GVL (Rutten et al ., , ) and GVHD (Stevanovic et al ., ) supporting the direct role of HLA‐DP proteins in the immune responses occurring between patient and donor cells post‐transplant.…”

Section: Unrelated Adult Donor Selectionmentioning

confidence: 97%

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

Little

Green

Harvey

et al. 2016

Int J Immunogenetics

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List of recommendations• All laboratories performing H&I testing for allogeneic HPC transplantation should follow EFI standards and be accreditated by EFI and UKAS/CPA. (Grade 1A)• HLA typing definitions as described by Nunes et al. 2011 and here should be used (Grade 1A)• HLA typing results should use official WHO HLA Nomenclature (Grade 1A)• The clinical urgency should be made available to the individual performing the related and unrelated donor search (Grade 1B)• HLA high resolution typing should be performed on potential matching; mismatching and haploidentical related donors when familial haplotypes cannot be fully assigned (Grade 1A)• Patients and selected related donors should be typed for HLA-A, -B, -C, -DRB1 and -DQB1 (+/-DPB1) (Grade 1A).• All patients and donors must have their HLA type confirmed on a second sample pre-transplant (Grade 1A).• The patient should be high resolution typed prior to submitting the HLA type for an unrelated donor search (Grade 1A)• A 10/10 high resolution HLA-A, -B, -C, -DRB1 and -DQB1 matched unrelated PBSC or bone marrow donor should be used where possible (Grade 1A).• Where a 10/10 matched PBSC or bone marrow donor is not available a single mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 is acceptable (Grade 1A).• Alternative progenitor cell donors (cord blood or haplo-identical) should be considered early in the donor search when a patient is unlikely to have an HLA matched unrelated donor (Grade 1A).• HLA-DRB3, -DRB4, -DRB5 typing should be performed and, when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, mismatches for these should be minimized (Grade 2A). • For unrelated donor selection, HLA-DPB1 typing should be performed and when a choice of otherwise equally matched and appropriate (e.g. CMV status) donors is available, non-permissive mismatches should be minimised (Grade 2C).• For mismatched related and unrelated donor selection, HVG mismatches are favoured over bi-directional and GVH mismatches (Grade 2C).• UCB units should be HLA typed to high resolution HLA-A, -B, -C, -DRB1, -DQB1 (Grade 1B ).• Selection of UCB units should follow national consensus guidelines published by Hough et al. (Grade 1A).• HLA alloantibody testing of the recipient should be performed at the time of donor search and should be repeated at the time of donor work-up request if an HLA mismatched donor is selected (Grade 1A).• The clinical team must be made aware of any HLA alloantibody incompatibility for a selected donor (Grade 1A).• When a choice of equally well matched donors is available, avoid selection of donors against which the patient has HLA alloantibodies (Grade 1A).• HLA alloantibody testing should be performed in cases of failed engraftment if the donor is HLA mismatched (Grade 1B).• The guideline published by Emery et al., 2013 recommending CMV matching between patient and donor should be followed (Grade 1A).• Major ABO incompatibilities should be avoided when there is a choice of HLA and CMV matched donors (Grade 1A)• Male donors ...

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“…A recent study has investigated the mismatch frequency of this locus, in sibling donors, and found it to be 5.31%. 8 HLA-DP incompatibility has previously been reported to be as high as 10.9% in siblings. 9 Studies, in unrelated donors, have investigated the probability of having a match at DP, when retrospective DNA typing on transplanted pairs has been performed, and the incidence of mismatching is reported at between 75 and 89%.…”

mentioning

confidence: 98%

The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

Shaw

Potter

Mayor

et al. 2003

Bone Marrow Transplant

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Summary:The importance of matching for HLA-DPB1 in unrelated donor haematopoietic stem cell (HSC) transplantation is little understood. Most transplant centres do not, currently, prospectively match for DPB1, but emerging data show that DPB1 matching does play a role in determining outcome. We studied the impact of HLA-DPB1 matching on outcome in 143 recipients of T-cell depletion transplants, who matched with their respective unrelated donors (allelic level) at HLA-A, -B, -C, -DRB1 and -DQB1. Of those matched at DPB1, 47.2% (17/36) developed acute graft-versus-host disease (aGvHD) as compared to 66.3% (55/83) of those who were mismatched. This led to a 19.1% (95% CI 0.1-38.3%) increase in the chance of developing aGvHD in mismatched patients (P ¼ 0.049). Relapse of the original disease occurred in 51 recipients; 23 of 37 (62%) matched at both DPB1 alleles, 28 of 82 (34%) were mismatched at one or two DPB1 alleles. Thus, there was a significantly higher relapse rate (P ¼ 0.0011) in transplant recipients who matched at both DPB1 alleles. In conclusion, a donor/recipient DPB1 match was associated with a significantly lower incidence of aGvHD and a significantly higher incidence of disease relapse. This study provides further evidence for an immunogenic role of HLA-DPB1 in HSC transplants.

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Frequency of HLA-DPB1 disparities detected by reference strand-mediated conformation analysis in HLA-A, -B, and -DRB1 matched siblings

Cited by 24 publications

References 17 publications

Resolution of complex feline leukocyte antigen DRB loci by reference strand‐mediated conformational analysis (RSCA)

Resolution of complex feline leukocyte antigen DRB loci by reference strand‐mediated conformational analysis (RSCA)

BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

The degree of matching at HLA-DPB1 predicts for acute graft-versus-host disease and disease relapse following haematopoietic stem cell transplantation

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