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Evolution of Antibodies to Epitopes of PE_PGRS51 in the Spectrum of Active Pulmonary Tuberculosis

Rama Murthy Sakamuri et al., Accepted manuscript (2019) - PMID: 31641771

Product(s) used in this publication:  Peptide ELISA

Abstract

BACKGROUND:

The PE_PGRS protein family isimplicated in virulence and immunopathogenesis of M. tuberculosis. Due to extensive intra-family homology, it has not been possible to correlate expression of specific members with stage of infection or disease progression. Here, we investigate the in vivo expression of PE_PGRS51, which besides the cross-reactive PE and PGRS domains, has 3 unique regions.

METHODS:

Expression in M. smegmatis confirmed PE_PGRS51 cell-wall localization. Patients at different stages of TB were classified across a spectrum akin to the Leprosy spectrum. Peptide arrays representing PE_PGRS51 were screened with sera from TB patients across the spectrum of active TB, with latent TB sera as controls.

RESULTS:

Antibodies directed only against conserved epitopes within the PE/PGRS domains were detectable at early stages of TB. As bacteriological burden and disease progresses, the epitope repertoire extends systematically to adjacent and overlapping peptides. Sera-reactivity to epitopes unique to PE_PGRS51 appear only in the most advanced TB patients, indicating PE_PGRS51 expression in vivo.

DISCUSSION:

The ability to classify active TB patients into a spectrum and delineate the in vivo expression of PE_PGRS proteins at different stages of disease has important implications for understanding their role in TB pathogenesis and their usefulness as diagnostic markers.

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