The utility of DLA typing for transplantation medicine in canine models

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.

[1]  T. Shiina,et al.  Evaluation of alloreactive T cells based on the degree of MHC incompatibility using flow cytometric mixed lymphocyte reaction assay in dogs , 2019, Immunogenetics.

[2]  M. B. Gugjoo,et al.  Mesenchymal stem cell basic research and applications in dog medicine , 2019, Journal of cellular physiology.

[3]  Jerzy K. Kulski,et al.  Identification of novel polymorphisms and two distinct haplotype structures in dog leukocyte antigen class I genes: DLA-88, DLA-12 and DLA-64 , 2018, Immunogenetics.

[4]  H. Onoe,et al.  MHC matching improves engraftment of iPSC-derived neurons in non-human primates , 2017, Nature Communications.

[5]  J. Powell,et al.  Murine Full-thickness Skin Transplantation. , 2017, Journal of visualized experiments : JoVE.

[6]  L. Schnabel,et al.  Allogeneic major histocompatibility complex‐mismatched equine bone marrow‐derived mesenchymal stem cells are targeted for death by cytotoxic anti‐major histocompatibility complex antibodies , 2016, Equine veterinary journal.

[7]  A. Zachary,et al.  HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act , 2016, Front. Immunol..

[8]  R. Kandaswamy,et al.  HLA‐A, ‐B, ‐C, ‐DR, and ‐DQ Matching in Pancreas Transplantation: Effect on Graft Rejection and Survival , 2016, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[9]  N. Pedersen,et al.  A genetic assessment of the English bulldog , 2016, Canine Genetics and Epidemiology.

[10]  E. Weil,et al.  OriginalClinicalScienceçGeneral The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors , 2016 .

[11]  G. Chambers,et al.  Recent Developments in Transplantation and Transfusion Medicine. , 2015, Annals of Transplantation.

[12]  D. Miklos,et al.  Clinical impact of H-Y alloimmunity , 2014, Immunologic research.

[13]  Min-Hee Kang,et al.  Evaluation of adverse reactions in dogs following intravenous mesenchymal stem cell transplantation , 2014, Acta Veterinaria Scandinavica.

[14]  J. Cates,et al.  Blood Group A antigen expression on cardiac endothelium is highly individualized: possible implications for transplantation. , 2013, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[15]  R. Storb,et al.  Safety of treatment with DLA-identical or unrelated mesenchymal stromal cells in DLA-identical canine bone marrow transplantation , 2013, Chimerism.

[16]  C. Gregory,et al.  Outcome after renal transplantation in 26 dogs. , 2012, Veterinary surgery : VS.

[17]  Harriet Noreen,et al.  High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. , 2007, Blood.

[18]  W. Ollier,et al.  Canine DLA diversity: 1. New alleles and haplotypes. , 2007, Tissue antigens.

[19]  R. Willemze,et al.  Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. , 2006, Blood.

[20]  A. Bartholomew,et al.  Immunologic Consequences of Multiple, High-Dose Administration of Allogeneic Mesenchymal Stem Cells to Baboons , 2006, Cell transplantation.

[21]  田中 友加 Low incidence of acute rejection after living-donor liver transplantation : immunologic analyses by mixed lymphocyte reaction using a carboxyfluorescein diacetate succinimidyl ester labeling technique , 2006 .

[22]  T. Asahara,et al.  Low Incidence of Acute Rejection after Living-Donor Liver Transplantation: Immunologic Analyses by Mixed Lymphocyte Reaction using a Carboxyfluorescein Diacetate Succinimidyl Ester Labeling Technique , 2005, Transplantation.

[23]  E. Kremmer,et al.  Minor Histocompatibility Antigens on Canine Hemopoietic Progenitor Cells1 , 2003, The Journal of Immunology.

[24]  Y. Yamaguchi,et al.  Histological features of renal allograft biopsies in ABO minor‐mismatched kidney transplantation , 2003, Clinical transplantation.

[25]  D. Sachs,et al.  Skin-specific alloantigens in miniature swine. , 2001, Transplantation.

[26]  E. Mignot,et al.  DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs. , 2000, Tissue antigens.

[27]  E. Dabelsteen,et al.  Tissue distribution of histo‐blood group antigens. , 2000, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[28]  R. Marquet,et al.  Electrophysiologic and histological monitoring of MHC-matched and mismatched canine intestinal allografts. , 1991, Journal of pediatric surgery.