title: Mixed chimeric hematopoietic stem cell transplant reverses the disease phenotype in canine leukocyte adhesion deficiency.
abstract: The genetic disease canine leukocyte adhesion deficiency (CLAD) is characterized by recurrent, severe bacterial infections, typically culminating in death by 6 months of age. CLAD is due to a mutation in the leukocyte integrin CD18 subunit, which prevents surface expression of the CD11/CD18 leukocyte integrin complex. We demonstrate that stable mixed donor:host hematopoietic chimerism, achieved by a non-myeloablative bone marrow transplant from a histocompatible littermate, reverses the disease phenotype in CLAD. Donor chimerism following the transplant was demonstrated both by flow cytometric detection of donor-derived CD18-positive leukocytes in the peripheral blood of the recipient, and by the demonstration of donor-derived DNA microsatellite repeats in the peripheral blood leukocytes of the recipient. These results indicate that mixed hematopoietic chimerism reverses the clinical phenotype in CLAD and represents a potential therapeutic approach for the human disease leukocyte adhesion deficiency.
authors.affiliation: Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Creevy
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bauer
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tuschong
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Embree
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Silverstone
authors.forename: John D
authors.initials: JD
authors.lastname: Bacher
authors.forename: Chris
authors.initials: C
authors.lastname: Romines
authors.forename: Julie
authors.initials: J
authors.lastname: Garnier
authors.forename: Marvin L
authors.initials: ML
authors.lastname: Thomas
authors.forename: Lyn
authors.initials: L
authors.lastname: Colenda
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Hickstein
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005434:Flow Cytometry / Q000662:veterinary; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000662:veterinary*; D007958:Leukocyte Count / Q000662:veterinary; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000628:therapy / Q000662:veterinary*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D018845:CD11 Antigens; D018821:CD18 Antigens; D004247:DNA