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Science 301 (5639): 1527-1530

Copyright © 2003 by the American Association for the Advancement of Science

Use of Genetic Profiling in Leprosy to Discriminate Clinical Forms of the Disease

Joshua R. Bleharski,1,2* Huiying Li,3* Christoph Meinken,4* Thomas G. Graeber,3* Maria-Teresa Ochoa,2 Masahiro Yamamura,5 Anne Burdick,6 Euzenir N. Sarno,7 Manfred Wagner,8 Martin Röllinghoff,4 Thomas H. Rea,9 Marco Colonna,10 Steffen Stenger,4 Barry R. Bloom,11 David Eisenberg,3 Robert L. Modlin1,2{ddagger}

Abstract: Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

1 Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
2 Division of Dermatology, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
3 Department of Chemistry and Biochemistry and Department of Biological Chemistry, Howard Hughes Medical Institute, UCLA–Department of Energy Institute of Genomics and Proteomics, UCLA, Los Angeles, CA 90095, USA.
4 Institut für Klinische Mikrobiologie, Immunologie, und Hygiene, Universität Erlangen, 91054 Erlangen, Germany.
5 Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan.
6 Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL33101, USA.
7 Leprosy Laboratory Institute Oswaldo Cruz, Rio de Janeiro, Brazil.
8 Medizinische Klinik 3, Klinikum Nürnberg, 90340 Nürnberg, Germany.
9 Section of Dermatology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
10 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
11 Office of the Dean, Harvard School of Public Health, Boston, MA 02115, USA.

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* These authors contributed equally to this work.

{ddagger} To whom correspondence should be addressed. E-mail: rmodlin{at}mednet.ucla.edu


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