Mixed chimeric hematopoietic stem cell transplant reverses the disease phenotype in canine leukocyte adhesion deficiency. Academic Article uri icon

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.

published proceedings

  • Vet Immunol Immunopathol

author list (cited authors)

  • Creevy, K. E., Bauer, T. R., Tuschong, L. M., Embree, L. J., Silverstone, A. M., Bacher, J. D., ... Hickstein, D. D.

citation count

  • 23

complete list of authors

  • Creevy, Kate E||Bauer, Thomas R||Tuschong, Laura M||Embree, Lisa J||Silverstone, Andrew M||Bacher, John D||Romines, Chris||Garnier, Julie||Thomas, Marvin L||Colenda, Lyn||Hickstein, Dennis D

publication date

  • October 2003