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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3582-3589. Prepublished online as a Blood First Edition Paper on January 8, 2004; DOI 10.1182/blood-2003-11-4008. This Article Full Text (PDF) All Versions of this Article: 2003-11-4008v1 103/9/3582    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bauer, T. R Articles by Hickstein, D. D Search for Related Content PubMed PubMed Citation Articles by Bauer, T. R Articles by Hickstein, D. D Social Bookmarking                   What's this? Submitted November 24, 2003 Accepted December 30, 2003 Very low levels of donor CD18+ neutrophils following allogeneic hematopoietic stem cell transplantation reverses the disease phenotype in canine leukocyte adhesion deficiency Thomas R Bauer*, Kate E Creevy, Yu-chen Gu, Laura M Tuschong, Robert E Donahue, Mark E Metzger, Lisa J Embree, Tanya Burkholder, John D Bacher, Chris Romines, Marvin L Thomas, Lyn Colenda, and Dennis D Hickstein Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA Hematology Branch, National Heart, Lung, Blood Institute, NIH, Rockville, MD, USA Office of Research Services, Veterinary Resources Program, NIH, Bethesda, MD, USA * Corresponding author; email: bauert{at}mail.nih.gov. Children with the severe phenotype of the genetic immunodeficiency disease leukocyte adhesion deficiency or LAD experience life-threatening bacterial infections due to 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 non-myeloablative hematopoietic stem cell transplants from normal matched littermates in nine dogs with the canine form of LAD known as CLAD, and demonstrate that in the three dogs with the lowest level of donor chimerism, less than 500 CD18+ donor-derived neutrophils per µL 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: W. Qasim, M. Cavazzana-Calvo, E. G. Davies, J. Davis, M. Duval, G. Eames, N. Farinha, A. Filopovich, A. Fischer, W. Friedrich, et al. Allogeneic Hematopoietic Stem-Cell Transplantation for Leukocyte Adhesion Deficiency Pediatrics, March 1, 2009; 123(3): 836 - 840. [Abstract] [Full Text] [PDF] Y. Tone, T. Wada, F. Shibata, T. Toma, Y. Hashida, Y. Kasahara, S. Koizumi, and A. Yachie Somatic revertant mosaicism in a patient with leukocyte adhesion deficiency type 1 Blood, February 1, 2007; 109(3): 1182 - 1184. [Abstract] [Full Text] [PDF] T. R. Bauer Jr, M. Hai, L. M. Tuschong, T. H. Burkholder, Y.-c. Gu, R. A. Sokolic, C. Ferguson, C. E. Dunbar, and D. D. Hickstein Correction of the disease phenotype in canine leukocyte adhesion deficiency using ex vivo hematopoietic stem cell gene therapy Blood, November 15, 2006; 108(10): 3313 - 3320. [Abstract] [Full Text] [PDF] T. H. Burkholder, L. Colenda, L. M. Tuschong, M. F. Starost, T. R. Bauer Jr, and D. D. Hickstein Reproductive capability in dogs with canine leukocyte adhesion deficiency treated with nonmyeloablative conditioning prior to allogeneic hematopoietic stem cell transplantation Blood, September 1, 2006; 108(5): 1767 - 1769. [Abstract] [Full Text] [PDF]

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