Antibodies to<i>Mycobacterium tuberculosis-specific</i>epitopes in lepromatous leprosy

Bothamley, GH; Beck, John S.; Britton, Warwick J.; Elsaghier, A.; Iványi, Juraj

doi:10.1111/j.1365-2249.1991.tb02948.x

Cited by 12 publications

(5 citation statements)

References 34 publications

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“…An alternate explanation is that active infection with M. lIeprae in patients previously exposed to M. tuberculosis stimulates cross-reactive helper T cells, which recall the antibody response of M. tuberculosis-specific memory B cells that have been primed through prior self-healing tuberculosis infection. This possibility is supported by the recent demonstration of antibodies to MAb-defined M. tuberculosis-specific epitopes in lepromatous leprosy patients in whom concomitant active tuberculosis had been carefully excluded (6).…”

Section: Discussionmentioning

confidence: 91%

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses

et al. 1992

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The 70-kDa heat shock protein ofMycobacterium leprae has a high degree of homology with the human hsp70 protein, yet it still elicits T-lymphocyte responses in subjects infected with M. leprae or vaccinated with the related Mycobacterium bovis BCG. We examined the serological responses to this protein by using recombinant protein fragments expressed from mutants with deletions of the M. leprae p70 gene. Monoclonal antibodies raised against either M. bovis or M. Ieprae p70 reacted with the C-terminal fragments but not the N-terminal fragments in a solid-phase enzyme-linked immunosorbent assay and an immunoblot assay. Inhibition enzyme-linked immunosorbent assays confirmed that two separate epitopes were defined by these monoclonal antibodies. Murine polyclonal sera also showed stronger binding to the C-terminal fragments. Sera from 33 and 48% of lepromatous leprosy patients reacted with M. leprae and M. bovis p70. This reactivity was mycobacterium specific, since few sera from control subjects in the same leprosy-endemic region were seropositive. The levels of anti-mycobacterial hsp70 antibodies were higher in patients with lepromatous leprosy than in those with tuberculoid leprosy or tuberculosis. The reactivity of sera from patients with leprosy was maximal with the C-terminal fragments. Therefore the C-terminal portion of M. keprae hsp70, which includes the region of maximum divergence from human hsp70, is the major target for the humoral immune response to the protein.

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Section: Discussionmentioning

confidence: 91%

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses

et al. 1992

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“…Although the diagnostic antigen of choice currently is undoubtedly the 38kDa protein, patients with lepromatous leprosy also show a considerable amount of anti-38kDa antibodies (19). The 19kDa protein is compromised by its cross-reactivity with M. avium (20), while the antibody to the 16kDa protein can also be identified in a significant fraction of infected healthy subjects.…”

Section: Immunodiagnostic Approachesmentioning

confidence: 99%

Diagnosis of tuberculosis: Available technologies, limitations, and possibilities

Garg

Tiwari

et al. 2003

Clinical Laboratory Analysis

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Rapid diagnosis and treatment are important for preventing transmission of Mycobacterium tuberculosis. However, the diagnosis of tuberculosis continues to pose serious problems, mainly because of difficulties in differentiating between patients with active tuberculosis and those with healed lesions, normal mycobacterium boris BCG (Bacillus Calmette Guerin) vaccinated individuals, and unvaccinated Manteux positives. Physicians still rely on conventional methods such as Ziehl-Neelsen (ZN) staining, fluorochrome staining, sputum culture, gastric lavage, and other non-traditional methods. Although the tuberculin test has aided in the diagnosis of tuberculosis for more than 85 years, its interpretation is difficult because sensitization with nontuberculous mycobacteria leads to false-positive tests. There have been numerous unsuccessful attempts to develop clinically useful serodiagnostic kits for tuberculosis. A number of proteinaceous and nonprotein antigens (such as acyltrehaloses and phenolglycolipids) have been explored from time to time for the development of such assays but they have not proved to be clinically useful. It has been difficult to develop an ELISA utilizing a suitable antigen because M. tuberculosis shares a large number of antigenic proteins with other microorganisms that may or may not be pathogenic. With the advent of molecular biology techniques, there have been significant advances in nucleic acid-based amplification and hybridization, which are helping to rectify existing flaws in the diagnosis of tuberculosis. The detection of mycobacterial DNA in clinical samples by polymerase chain reaction (PCR) is a promising approach for the rapid diagnosis of tuberculous infection. However, the PCR results must be corrected for the presence of inhibitors as well as for DNA contamination. In the modern era of genetics, marked by proteomics and genomics, the day is not far off when DNA chip-based hybridization assays will instantly reveal mycobacterial infections.

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“…However, for protein antigens, antibody to the Mtb-specific epitopes could be detected in sera from patients with leprosy, although no antibody to the leprosy-specific ML04 epitope (35-kDa antigen) was found in TB patients ( 32 ). Two explanations exist for this finding.…”

Section: Epitope-specific Antibody In Leprosymentioning

confidence: 97%

Epitope-Specific Antibody Levels in Tuberculosis: Biomarkers of Protection, Disease, and Response to Treatment

Bothamley

2014

Front. Immunol.

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Monoclonal antibodies restricted to Mycobacterium tuberculosis can measure epitope-specific antibody levels in a competition assay. Immunodominant epitopes were defined from clinical samples and related to the clinical spectrum of disease. Antibody to the immunodominant epitopes was associated with HLA-DR15. Occupational exposure showed a different response and was consistent with recognition of dormancy-related proteins and protection despite exposure to tuberculosis (TB). Studies in leprosy revealed the importance of immune deviation and the relationships between T and B cell epitopes. During treatment, antibody levels increased, epitope spreading occurred, but the affinity constants remained the same after further antigen exposure, suggesting constraints on the process of epitope selection. Epitope-specific antibody levels have a potential role as biomarkers for new vaccines which might prevent the progression of latent to active TB and as tools to measure treatment effects on subpopulations of tubercle bacilli.

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Antibodies toMycobacterium tuberculosis-specificepitopes in lepromatous leprosy

Cited by 12 publications

References 34 publications

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses

The variable C-terminal region of the Mycobacterium leprae 70-kilodalton heat shock protein is the target for humoral immune responses

Diagnosis of tuberculosis: Available technologies, limitations, and possibilities

Epitope-Specific Antibody Levels in Tuberculosis: Biomarkers of Protection, Disease, and Response to Treatment

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