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

Abstract

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.

Antibodies and tuberculosis

“…Here an IgA gene rearrangement of VH3-23-D3-3-J4 was predominant amongst those nurses who remained TST-negative and did not develop active disease compared to their TST reactive colleagues [43]. An earlier study of nurses exposed to TB revealed a strong antibody response against a non-immunodominant epitope of Acr [44]. A possible conclusion of such studies is that these individuals produce antibodies against M.tb that prevent or help resolve infection despite high exposure to the bacillus…”

“…Lack of antibodies against LAM, membrane vesicles and 38-kDa antigen associated with risk of extra-pulmonary disease [34], [36], [44]…”

Fusion of selected regions of mycobacterial antigens for enhancing sensitivity in serodiagnosis of tuberculosis

“…It is specific only to the cavitary TB patients (Samanich et al, 2001;Sartain et al, 2006). Several overlapping epitopes of PstS1 have been analyzed (Baassi et al, 2009;Gaseitsiwe et al, 2008;Harris et al, 1996;Jackett et al, 1988;Landowski et al, 2001;Lopez-Vidal et al, 2004) and epitope-specific antibody detection correlates well with antibody levels to the purified antigen (Bothamley, 2014).…”

Significance of Antigen and Epitope Specificity in Tuberculosis

“…Although these cytokines are produced by several cell types [CD4, CD8, TCRγδ, mucosa-associated invariant T cells (MAIT), CD1-restricted T cells, and natural killer (NK) cells], it is significant that CD4 T cell depletion cannot be compensated with cell types other than CD4 T cells. Epitope-specific serum antibody levels in TB patients have been found to be influenced by the pulmonary bacterial load (associated with HLA-DR15), recent exposure to infection, and response to chemotherapy ( 5 ).…”