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Pre-Clinical Studies

Conversion of the severe to the moderate disease phenotype with donor leukocyte microchimerism in canine leukocyte adhesion deficiency

Bone Marrow Transplantation volume 37, pages 607–614 (2006)Cite this article

Abstract

Leukocyte adhesion deficiency-1 (LAD-1), a genetic immunodeficiency disease characterized by life-threatening bacterial infections, results from the defective adherence and migration of leukocytes due to mutations in the leukocyte integrin CD18 molecule. Canine LAD (CLAD) represents the canine homologue of the severe phenotype of LAD-1 in children. In previous studies we demonstrated that non-myeloablative stem cell transplantation from matched littermates resulted in mixed donor–host chimerism and reversal of the disease phenotype in CLAD. In this study, we describe two CLAD dogs with less than 2% donor leukocyte chimerism following non-myeloablative transplant. Both dogs are alive more than 24 months after transplant with an attenuated CLAD phenotype resembling the moderate deficiency phenotype of LAD. The improvement in the CLAD phenotype with very low levels of donor CD18+ leukocytes correlated with the preferential egress of the CD18+ neutrophils into extravascular sites. The clinical response with very low levels of donor CD18+ leukocytes in CLAD supports using this model for testing gene therapy strategies since the low levels of gene-corrected hematopoietic cells expected with hematopoietic gene therapy would likely have a therapeutic effect in CLAD.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Y-C Gu, T R Bauer, R A Sokolic, M Hai, L M Tuschong & D D Hickstein

  2. Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, MD, USA

    T Burkholder, J Bacher & M F Starost

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  1. Y-C Gu
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  2. T R Bauer
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  3. R A Sokolic
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  4. M Hai
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  5. L M Tuschong
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  6. T Burkholder
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  7. J Bacher
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  8. M F Starost
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  9. D D Hickstein
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Correspondence to Y-C Gu.

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Gu, YC., Bauer, T., Sokolic, R. et al. Conversion of the severe to the moderate disease phenotype with donor leukocyte microchimerism in canine leukocyte adhesion deficiency. Bone Marrow Transplant 37, 607–614 (2006). https://doi.org/10.1038/sj.bmt.1705291

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