Latent TB diagnosis: A correlation between molecular and immunological biomarkers
Author(s): Vivek Nair 1, Sheetal Kaul 1, Shikha Dhawan 2, Pawan Malhotra 1, Shammim Mannan 3, Kirankumar Rade 4, Ashwani Khanna 5, Asif Mohammed 1
1) International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
2) Partasia Biopharm, New Delhi, India.
3) Independent TB Consultant, New Delhi, India.
4) WHO-India Country Office, New Delhi, India.
5) RNTCP, New Delhi, India.
A quarter of the world’s population is estimated to play host to Mycobacterium tuberculosis (MTB) in the form of latent TB infection (LTBI). The diagnosis of LTBI is not straightforward and can be performed using either Tuberculin skin test (TST) or IFN-γ release assay (IGRA), which have several limitations including low sensitivity and specificity. Recently, gene signatures measuring host immune response to MTB in blood samples have been proposed. The objective of the study is to assess correlation between immunological markers and molecular markers associated with LTBI. Household contacts of bacteriologically confirmed active pulmonary TB cases (drug sensitive and drug resistant) were recruited for the study. Whole blood samples were collected from the contacts. Chest X-ray (CXR)/GeneXpert was used to rule out active TB cases in contacts. The contacts were screened using QuantiFERON-TB Gold Plus (QFT) to perform IGRA. Out of the 81 household contacts included in our study, there were ~54% IGRA positive cases and ~46% IGRA negative cases. Total RNA was extracted from whole blood and was used for qPCR assay to quantitate expression levels of 6 gene signature to differentiate between LTBI (IGRA +ve) and healthy (IGRA -ve) cases.
To correlate molecular and immunological markers linked with LTBI cases, IGRA data and gene expression profiles from each sample was analyzed. Our data suggests that a combination of molecular and immunological markers can be more useful for defining LTBI cases.