Mixed chimeric hematopoietic stem cell transplant reverses the disease phenotype in canine leukocyte adhesion deficiency.
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.
Creevy
Kate E
KE
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Bauer
Thomas R
TR
Tuschong
Laura M
LM
Embree
Lisa J
LJ
Silverstone
Andrew M
AM
Bacher
John D
JD
Romines
Chris
C
Garnier
Julie
J
Thomas
Marvin L
ML
Colenda
Lyn
L
Hickstein
Dennis D
DD
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*
D018952:Antigens, CD34; D018845:CD11 Antigens; D018821:CD18 Antigens; D004247:DNA