Leprosy is a chronic infectious disease prevalent in underdeveloped countries. There are thought to be 15 million cases worldwide of which 5 million are confirmed. Leprosy presents many immunological problems, but 3 major ones have been identified by WHO. 1. The diagnosis of leprosy using immunological methods. 2. The development of a prophylactic vaccine, and 3. Elucidation of the immunological factors which underly various complications of leprosy, including peripheral neuropathy and anergy. We have developed a research program that is addressed to the first and third of these problems. Projects 1 and 2 are concerned with diagnosis of leprosy. The first project seeks to identify in the urine of leprosy patients both mycobacterial antigens and host products that are generated in response to leprosy infection. It is hoped to develop a simple urine test for leprosy that would be applicable to large scale diagnostic and epidemiologic studies. The second project is concerned with the use of delayed hypersensitivity skin (DTH) reactions in leprosy. The kinetics and immunocytochemistry of DTH reactions to soluble M. leprae antigens will be studied to discover the potential diagnostic value of such tests, their prognostic significance, and the immunological mechanisms that determine the type of DTH reaction. Project 3 is based on the hypothesis that some of the manifestations of leprosy neuropathy are mediated by autoimmune mechanisms. To this end immunocytochemistry will be used to study binding of suspected autoantibodies to diseased and normal nerves; and to measure nerve-antigen-specific antibodies in the serum. Project 4 seeks to uncover the presence of M. leprae-reactive T cells in anergic patients by the application of limiting dilution and T cell cloning techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI020198-03
Application #
3091607
Study Section
Microbiology and Infectious Diseases Research Committee (MID)
Project Start
1984-02-01
Project End
1989-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Near, K A; Lefford, M J (1992) Use of serum antibody and lysozyme levels for diagnosis of leprosy and tuberculosis. J Clin Microbiol 30:1105-10
Mahon, A C; Nurlign, A; Kebede, B et al. (1991) Urinary phenolic glycolipid 1 in the diagnosis and management of leprosy. J Infect Dis 163:653-6
Lefford, M J; Hunegnaw, M; Siwik, E (1991) The value of IgM antibodies to PGL-I in the diagnosis of leprosy. Int J Lepr Other Mycobact Dis 59:432-40
Ab, B K; Kiessling, R; Van Embden, J D et al. (1990) Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein. Eur J Immunol 20:369-77
Ottenhoff, T H; Converse, P J; Gebre, N et al. (1989) T cell responses to fractionated Mycobacterium leprae antigens in leprosy. The lepromatous nonresponder defect can be overcome in vitro by stimulation with fractionated M. leprae components. Eur J Immunol 19:707-13
Benjamins, J A; Callahan, R E; Runft, D et al. (1989) Anti-neural antibodies in leprosy sera: further characterization of the antigens. J Neuroimmunol 21:125-35
Ottenhoff, T H; Ab, B K; Van Embden, J D et al. (1988) The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette-Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes. J Exp Med 168:1947-52
Converse, P J; Ottenhoff, T H; Gebre, N et al. (1988) Cellular, humoral, and gamma interferon responses to Mycobacterium leprae and BCG antigens in healthy individuals exposed to leprosy. Scand J Immunol 27:515-25
Ehrenberg, J P; Gebre, N (1987) Analysis of the antigenic profile of Mycobacterium leprae: cross-reactive and unique specificities of human and rabbit antibodies. Scand J Immunol 26:673-81
Kaldany, R R; Maasho, K; Ohman, R et al. (1987) Methods for the detection of a specific Mycobacterium leprae antigen in the urine of leprosy patients. Scand J Immunol 25:37-43

Showing the most recent 10 out of 12 publications