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Blood. 2004 May 1;103(9):3582-9. Epub 2004 Jan 8.

Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverse the disease phenotype in canine leukocyte adhesion deficiency.

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1
Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg 10, Rm 12C-116, 10 Center Dr, MSC1907, Bethesda, MD 20892-1907, USA. bauert@mail.nih.gov

Abstract

Children with the severe phenotype of the genetic immunodeficiency disease leukocyte adhesion deficiency or LAD experience life-threatening bacterial infections because of molecular defects in the leukocyte integrin CD18 molecule and the resultant failure to express the CD11/CD18 adhesion molecules on the leukocyte surface. Hematopoietic stem cell transplantation remains the only definitive therapy for LAD; however, the degree of donor chimerism and particularly the number of CD18(+) donor-derived neutrophils required to reverse the disease phenotype are not known. We performed nonmyeloablative hematopoietic stem cell transplantations from healthy matched littermates in 9 dogs with the canine form of LAD known as CLAD and demonstrate that in the 3 dogs with the lowest level of donor chimerism, less than 500 CD18(+) donor-derived neutrophils/microL in the peripheral blood of the CLAD recipients resulted in reversal of the CLAD disease phenotype. These results demonstrate the value of a disease-specific, large-animal model for identifying the lowest therapeutic level required for successful cellular and gene therapy.

PMID:
14715622
DOI:
10.1182/blood-2003-11-4008
[Indexed for MEDLINE]
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