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* Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523;
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom;
Laboratory Research Branch, Division of the National Hansen’s Disease Programs, Louisiana State University, Baton Rouge, LA 70803;
Laboratory of Cellular Microbiology and
¶ Leprosy Laboratory, Department of Mycobacterial Diseases, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil;
|| Laboratory of Immunopathology and
# Laboratory of Medical Informatics, School of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil;
** Department of Medical Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil;
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands;
* Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea;
* Department of Pathology and Infectious Diseases, Royal Veterinary College, London, United Kingdom; and
* Unité de Génétique Moléculaire Bacterienne, Institut Pasteur, Paris, France
Diagnosis of leprosy is a major obstacle to disease control and has been compromised in the past due to the lack of specific reagents. We have used comparative genome analysis to identify genes that are specific to Mycobacterium leprae and tested both recombinant proteins and synthetic peptides from a subset of these for immunological reactivity. Four unique recombinant proteins (ML0008, ML0126, ML1057, and ML2567) and a panel of 58 peptides (15 and 9 mer) were tested for IFN-
responses in PBMC from leprosy patients and contacts, tuberculosis patients, and endemic and nonendemic controls. The responses to the four recombinant proteins gave higher levels of IFN- production, but less specificity, than the peptides. Thirty-five peptides showed IFN- responses only in the paucibacillary leprosy and household contact groups, with no responses in the tuberculosis or endemic control groups. High frequencies of IFN--producing CD4+ and CD8+ T cells specific for the 15- and 9-mer peptides were observed in the blood of a paucibacillary leprosy patient. 9-mer peptides preferentially activated CD8+ T cells, while the 15-mer peptides were efficient in inducing responses in both the CD4+ and CD8+ T cell subsets. Four of the six 9-mer peptides tested showed promising specificity, indicating that CD8+ T cell epitopes may also have diagnostic potential. Those peptides that provide specific responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of M. leprae infection and epidemiological surveys of the incidence of leprosy, of which little is known.
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