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Blood, 1 January 2008, Vol. 111, No. 1, pp. 209-218. Prepublished online as a Blood First Edition Paper on September 17, 2007; DOI 10.1182/blood-2007-04-082552. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-04-082552v1 111/1/209    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Uzel, G. Articles by Holland, S. M. Search for Related Content PubMed PubMed Citation Articles by Uzel, G. Articles by Holland, S. M. Related Collections Cell Adhesion and Motility Clinical Trials and Observations Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1) Gulbu Uzel1, Emilia Tng2, Sergio D. Rosenzweig3, Amy P. Hsu1, Jacqueline M. Shaw2, Mitchell E. Horwitz4, Gilda F. Linton5, Stacie M. Anderson6, Martha R. Kirby6, Jaõ B. Oliveira7, Margaret R. Brown7, Thomas A. Fleisher7, S. K. Alex Law2,8, and Steven M. Holland1 1 Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD; 2 Medical Research Council (MRC) Immunohistochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, United Kingdom; 3 Servicio de Inmunologia, Hospital Nacional de Pediatria J. P. Garrahan, Buenos Aires, Argentina; 4 Department of Medicine, Duke University Medical Center, Durham, NC; 5 Laboratory of Host Defenses, NIAID, NIH, Bethesda, MD; 6 Genetics and Molecular Biology Branch, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD; 7 Immunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, MD; and 8 School of Biological Sciences, Nanyang Technological University, Singapore Leukocyte adhesion deficiency type-1 (LAD-1) is an autosomal recessive immunodeficiency caused by mutations in the β2 integrin, CD18, that impair CD11/CD18 heterodimer surface expression and/or function. Absence of functional CD11/CD18 integrins on leukocytes, particularly neutrophils, leads to their incapacity to adhere to the endothelium and migrate to sites of infection. We studied 3 LAD-1 patients with markedly diminished neutrophil CD18 expression, each of whom had a small population of lymphocytes with normal CD18 expression (CD18+). These CD18+ lymphocytes were predominantly cytotoxic T cells, with a memory/effector phenotype. Microsatellite analyses proved patient origin of these cells. Sequencing of T-cell subsets showed that in each patient one CD18 allele had undergone further mutation. Interestingly, all 3 patients were young adults with inflammatory bowel disease. Somatic reversions of inherited mutations in primary T-cell immunodeficiencies are typically associated with milder clinical phenotypes. We hypothesize that these somatic revertant CD18+ cytotoxic T lymphocytes (CTLs) may have altered immune regulation. The discovery of 3 cases of reversion mutations in LAD-1 at one center suggests that this may be a relatively common event in this rare disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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