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

doi:10.1126/science.1087785

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Science 12 September 2003:
Vol. 301. no. 5639, pp. 1527 - 1530
DOI: 10.1126/science.1087785

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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

Leprosy presents as a clinical and immunological spectrum ofdisease. With the use of gene expression profiling, we observedthat a distinction in gene expression correlates with and accuratelyclassifies the clinical form of the disease. Genes belongingto the leukocyte immunoglobulin-like receptor (LIR) family weresignificantly up-regulated in lesions of lepromatous patientssuffering from the disseminated form of the infection. In functionalstudies, LIR-7 suppressed innate host defense mechanisms byshifting monocyte production from interleukin-12 toward interleukin-10and by blocking antimicrobial activity triggered by Toll-likereceptors. Gene expression profiles may be useful in definingclinical forms of disease and providing insights into the regulationof 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.

^* These authors contributed equally to this work.

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

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