Dataset Information

The utility of DLA typing for transplantation medicine in canine models.

ABSTRACT: Transplantation medicine is used for the treatment of severe canine diseases, and the dog leukocyte antigen (DLA) is considered to be important in graft rejection. However, the utility of direct sequencing of both DLA classes I and II has not been assessed thoroughly. Eight healthy beagles with identified DLA genes were divided into two sets of four dogs, each including one donor and three recipients for skin transplantation. The following recipients were selected: one dog with a complete match, one with a haploidentical match, and one with a complete mismatch of the DLA gene with the donor. Full-thickness skin segments were obtained from each donor and transplanted to the recipients. A mixed lymphocyte reaction (MLR) assay was performed and analyzed by flow cytometry. Skin grafts of DLA haploidentical and mismatched pairs were grossly rejected within 14 days, whereas in fully matched DLA pairs, survival was as long as 21 days. Histopathological evaluation also showed moderate to severe lymphocytic infiltration and necrosis in DLA mismatched pairs. As seen in the MLR assay, the stimulation index of DLA mismatched pairs was significantly higher than that of fully matched DLA pairs in both sets (P<0.001). The allogeneic transplantation results suggested that it is possible to prolong transplant engraftment by completely matching the DLA genotype between the donor and recipient. Additionally, the MLR assay may be used as a simplified in vitro method to select donors.

SUBMITTER: Sato K

PROVIDER: S-EPMC7468067 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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The utility of DLA typing for transplantation medicine in canine models.

Sato Keita K Miyamae Jiro J Sakai Manabu M Okano Masaharu M Katakura Fumihiko F Shibuya Hisashi H Nakayama Tomohiro T Moritomo Tadaaki T

The Journal of veterinary medical science 20200706 8

Transplantation medicine is used for the treatment of severe canine diseases, and the dog leukocyte antigen (DLA) is considered to be important in graft rejection. However, the utility of direct sequencing of both DLA classes I and II has not been assessed thoroughly. Eight healthy beagles with identified DLA genes were divided into two sets of four dogs, each including one donor and three recipients for skin transplantation. The following recipients were selected: one dog with a complete match, ...[more]

PMID: 32624549

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Project description:BackgroundCanine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes.MethodsThe 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs were genotyped for allelic variation at DLA-DRB1, -DQA1, -DQB1 loci using DNA sequence-based typing. Genotypes from all three loci were combined to reveal three-locus DLA class II haplotypes, which were evaluated for statistical associations with DM. This was performed for each breed individually and for all breeds pooled together.ResultsFive dog breeds were identified as having one or more DLA haplotype associated with DM susceptibility or protection. Four DM-associated haplotypes were identified in the Cocker Spaniel breed, of which one haplotype was shared with Border Terriers. In the three breeds known to be at highest risk of DM included in the study (Samoyed, Tibetan Terrier and Cairn Terrier), no DLA haplotypes were found to be associated with DM.ConclusionsNovel DLA associations with DM in specific dog breeds provide further evidence that immune response genes contribute susceptibility to this disease in some cases. It is also apparent that DLA may not be contributing obvious or strong risk for DM in some breeds, including the seven breeds analysed for which no associations were identified.

Dataset Information

The utility of DLA typing for transplantation medicine in canine models.

Publications

The utility of DLA typing for transplantation medicine in canine models.

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