Detection of anti-HspX antibodies and HspX protein in patient sera for the identification of recent latent infection by Mycobacterium tuberculosis

• Authors: Jorge Castro-Garza, Instituto Mexicano del Seguro Social; Paola Garcia-Jacobo, Instituto Mexicano del Seguro Social; Lydia G. Rivera-Morales, Universidad Autónoma de Nuevo León; Frederick D. Quinn, University of Georgia; James Barber, University of Georgia; Russell Karls, University of Georgia; Debra Haas, University of Georgia; Shelly Helms, University of Georgia; Tuhina Gupta, University of Georgia; Henry Blumberg, Emory University; Jane Tapia, Emory University; Itza Luna-Cruz, Universidad Autónoma de Nuevo León; Adrian Rendon, Universidad Autónoma de Nuevo León; Javier Vargas-Villarreal, Instituto Mexicano del Seguro Social; Lucio Vera-Cabrera, Universidad Autónoma de Nuevo León; Cristina Rodriguez-Padilla, Universidad Autónoma de Nuevo León
• Journal Title: PLoS ONE
• Volume: Volume 12, Number 8
• Publisher: Public Library of Science | 2017-08-16, Pages e0181714-e0181714
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1371/journal.pone.0181714
• Subjects: Health Sciences, Immunology; Biology, Microbiology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; IMMUNE-RESPONSES; RECOGNITION; EXPRESSION; DIAGNOSIS; BOVIS; CATTLE; GENES; TESTS; BCG; Mycobacterium tuberculosis; Enzyme-linked immunoassays; Tuberculosis; Serum proteins; Antibodies; Tuberculosis diagnosis; Mycobacterium bovis; Recombinant proteins

Abstract

Mycobacterium tuberculosis is a pathogen causing tuberculosis (TB) a spectrum of disease including acute and asymptomatic latent stages. Identifying and treating latently-infected patients constitutes one of the most important impediments to TB control efforts. Those individuals can remain undiagnosed for decades serving as potential reservoirs for disease reactivation. Tests for the accurate diagnosis of latent infection currently are unavailable. HspX protein (α-crystallin), encoded by Rv2031c gene, is produced in vitro by M. tuberculosis during stationary growth phase and hypoxic or acidic culture conditions. In this study, using standard, and Luminex xMAP® bead capture ELISA, respectively, we report on detection of anti-HspX IgG and IgM antibodies and HspX protein in sera from acute and latent TB patients. For the antibody screen, levels of IgG and IgM antibodies were similar between non-infected and active TB patients; however, individuals classified into the group with latent TB showed higher values of anti-HspX IgM (p = 0.003) compared to active TB patients. Using the bead capture antigen detection assay, HspX protein was detected in sera from 56.5% of putative latent cases (p< 0.050) compared to the background median with an average of 9,900 pg/ml and a range of 1,000 to 36,000 pg/ml. Thus, presence of anti-HspX IgM antibodies and HspX protein in sera may be markers of latent TB.