PPE17 (Rv1168c) protein of Mycobacterium tuberculosis detects individuals with latent TB infection

PLoS One. 2018 Nov 26;13(11):e0207787. doi: 10.1371/journal.pone.0207787. eCollection 2018.

Abstract

Latent tuberculosis infection (LTBI) is a clinically distinct category of Mycobacterium tuberculosis (Mtb) infection that needs to be diagnosed at the initial stage. We have reported earlier that one of the Mtb proline-proline-glutamic acid (PPE) proteins, PPE17 (Rv1168c) is associated with stronger B-cell and T-cell responses and could be used to diagnose different clinical categories of active TB patients with higher specificity and sensitivity than PPD and ESAT-6. Based on these observations we further tested the potential of PPE17 for the diagnosis of LTBI. We tested 198 sera samples collected from LTBI individuals (n = 61), QFT-negative (n = 58) and active TB patients (n = 79). Individuals were defined as LTBI by QuantiFERON-TB Gold In-Tube test (QFT-GIT) positive results, while active TB patients were confirmed based on the guidelines of the Revised National TB Control Programme of India. The antibody responses against PPE17, ESAT-6:CFP-10 and PPD were compared in these subjects by enzyme-linked immunosorbent assay. We observed that LTBI individuals show a higher sero-reactivity to PPE17 as compared to currently used latent TB diagnostic antigens like ESAT-6, CFP-10 and PPD. The LTBI and active TB patients display almost similar sensitivity. Interestingly, PPE17 could discriminate LTBI positive subjects from the QFT-negative subjects (P < 0.001). Our study hints that PPE17 may be used as a novel serodiagnostic marker to screen the latently infected subjects and may also be used as a complimentary tool to the QFT-GIT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / immunology
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biomarkers / metabolism
  • Female
  • Humans
  • Latent Tuberculosis / diagnosis*
  • Latent Tuberculosis / immunology
  • Male
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / metabolism
  • Mycobacterium tuberculosis / physiology*
  • Protein Domains
  • Serologic Tests

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • Biomarkers

Grants and funding

This study was supported by the Department of Biotechnology (BT/PR20669/MED/29/1072/2016), Government of India to SM. PRA was supported by the Research Associateship from the Indian Council of Medical Research, Government of India (80/796/2013-ECD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.