PpiA antigen specific immune response is a potential biomarker for latent tuberculosis infection

Abstract

One third of the world's population is estimated to harbour latent tuberculosis infection (LTBI). Around 10% of them have the life time risk of developing active tuberculosis (PTB). Currently there is no gold standard test for identifying LTBI. Therefore identification of specific markers for LTBI will help as to develop a test specific for LTBI. Earlier, in our immunoproteomic analysis, we found that peptidyl-prolyl cis-trans isomerase A (PpiA) protein-containing fractions induced significantly higher interferon-gamma (IFN-γ) response in LTBI than in PTB. Immunological characterisation of recombinant PpiA protein was carried out in the current study. We have studied 10 cytokines and 2 chemokine responses against PpiA and standard antigens such as early secretory antigenic target-6 (ESAT-6) and culture filtrate antigen-10 (CFP-10). In healthy household contacts (HHC), all the tested antigens induced significantly higher levels of IFN-γ and Interlukin-8 (IL-8) compared with those in PTB. PpiA-specific IL-12p40 response was significantly increased in HHC compared with that in PTB. PpiA antigen-specific IFN-γ and IL-12p40 both showed 86% positivity in HHC, whereas in PTB, they showed 20% and 38% positivity, respectively. In terms of IFN-γ/TNF-α ratio, PpiA displayed 86% (30/35) positivity in HHC and 18% (7/39) positivity in PTB. In summary we found that PpiA-specific IFN-γ and IFN-γ/TNF-α ratio response were specific biomarkers for LTBI identification.

Keywords: Biomarker; Household contacts; Interferon-γ; Latent tuberculosis; Pulmonary TB patients; Tumour necrosis factor-α.