Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-11-20
1998-10-06
Housel, James C.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
4241631, 4241681, 4242481, 435 71, 4351723, 4352531, G01N 3353
Patent
active
058174737
DESCRIPTION:
BRIEF SUMMARY
The invention relates to a method for identifying a Mycobacterium species responsible for a mycobacterial infection in human or animal. The invention further relates to diagnostic kits for use in the method.
The genus Mycobacterium which contains about 50 species is responsible for a number of human and animal diseases which are known collectively as the mycobacterioses. The best known of these in humans is leprosy, caused by M. leprae, which affects more than ten million people worldwide, and tuberculosis, usually caused by M. tuberculosis, at least ten million new cases of which occur each year. Most other mycobacteria normally occur only as environmental saprophytes but can also cause opportunist diseases. This happens usually, but not only, in the case of people who have problems with their immune system, such as AIDS patients and people undergoing immunosuppression. These opportunist types comprise the slow-growing species M. avium, and the closely related M. intracellulare and M. scrofulaceum (often referred to together as MAIS complex), M. kansasi, M. marinum and M. ulcerans, and the fast-growing species M. chelonae and M. fortuitum. Although once rare, the incidence of opportunist mycobacterial diseases and tuberculosis shows a parallel increase in the western world with the incidence of AIDS. In addition there is limited but increasing evidence that mycobacteria or antigens thereof play a direct or indirect part in the etiology of a plurality of other diseases such as sarcoidosis and Crohn's disease and different auto-immune diseases such as auto-immune dermatitis, rheumatoid arthritis and diabetes. This could be attributed to a structural mimicry between epitopes of mycobacteria and those of the host.
The cell walls of mycobacteria are very complex and contain many lipids, some with structures unique to the genus. These structures comprise mycolinic acids and esters, peptido-glycolipide, arabino-galactane and lipo-arabino-manane. The lipid-rich mycobacterial cell walls are responsible for the characterizing colouring properties of the mycobacteria. They also enable mycobacteria to counter an attack by the immune system of the host. A number of species, once taken up into macrophages, are capable of surrounding themselves with a thick layer of secreted lipids.
Many different components of the mycobacteria begin an interaction with the immune system. These components comprise protein and hydrocarbon antigens, which can either be actively secreted by the mycobacteria or can form part of the cell wall or cell membrane. In addition they may be present in the cytoplasm, for instance in the cytoplasmic matrix, ribosomes and enzymes. Mycobacteria also possess immuno-modulating components such as immunosuppressing compounds and adjuvants. Consequently, a single mycobacterial species can induce a large variety of immune responses in different forms and with diverse specificities. It is therefore difficult to distinguish immune responses against species-specific components from cross reactions. For this reason it has therefore been found difficult to derive protein antigens suitable for the detection of species-specific humoral responses as a basis for a very sensitive and specific sero-diagnostic test for tuberculosis. Because the mycobacteria occur a great deal in the environment, human serum nearly always contains anti-mycobacterial antibodies.
In view of the problems with the specificity of protein antigens, a number of researchers, including the present inventors, have focused their attention on species-specific glycolipid antigens for the detection of specific humoral immune responses. Although the immune reactivity against mycobacteria is of the cell-mediated type and the humoral immune responses probably play a minor part in the total effector mechanism of mycobacterial immunity and immunopathology, studies into the antibody response to immuno-dominant mycobacterial cross-reactive antigen components (further referred to as Im-CRAC) could shed light on the varying capability of the host to recognize
REFERENCES:
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Vega-Lopez, F. et al., "Recognition of Mycobacterial Antigens by Sera from Patients with Leprosy." Journal of Clinical Microbiology, vol. 26, No. 12, 1 Dec. 1988.
Roche, P.W. et al., "Antibody Repsonses to the 18-kDa Protein of Mycobacterium Leprae in Leprosy and Tuberculosis Patients". International Journal of Leprosy, vol. 60, No. 2, 1 Jun. 1992.
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Das Pranab Khumar
Houthoff Hendrik Jan
Van Es Remco Maria
Housel James C.
Kreatech Biotechnology B.V.
Swartz Rodney P.
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