title: The assessment of cytokines in Quantiferon supernatants for the diagnosis of latent TB infection in a tribal population of Melghat, India.
abstract: The tuberculin skin test (TST) and interferon-gamma release assays (IGRA), namely, the QuantiFERON-TB Gold test (QFT), remain the standard immunological diagnostic tools for latent tuberculosis (TB) infection (LTBI). However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ) as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i) QFT+/TST+ (n = 26), (ii) QFT+/TST- (n = 12), (iii) QFT-/TST- (n = 35) and (iv) QFT-/TST+ (n = 1) groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R) was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT-/TST- group. Correlation analysis identified a positive correlation between IL-6 and the QFT response (r = 0.6723, P < 0.0001), while a negative correlation was seen between QFT and IL-10 expression (r = -0.3271, P = 0.0044). Similarly, IL-6 was positively correlated with TST levels (r = 0.6631, P <0 .0001), and conversely, a negative correlation was found between TST and IL-10 expression (r = -0.5698, P < 0.0001). The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection accuracy of LTBI. Our observations require investigation in larger well-characterized cohorts along with follow-up studies to further confirm the study outcome.
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Prachi R
authors.initials: PR
authors.lastname: Bapat
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Aliabbas A
authors.initials: AA
authors.lastname: Husain
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Hatim F
authors.initials: HF
authors.lastname: Daginawala
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Neha P
authors.initials: NP
authors.lastname: Agrawal
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Milind S
authors.initials: MS
authors.lastname: Panchbhai
authors.affiliation: Meditation, AIDS, Health, Addiction & Nutrition (MAHAN) Trust, C/O Mahatma Gandhi Tribal Hospital, Karmagram, Utavali, Tahsil Dharni, Amravati, Maharashtra, India.
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Satav
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
authors.forename: Girdhar M
authors.initials: GM
authors.lastname: Taori
authors.affiliation: Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India. Electronic address: raj_ciims@rediffmail.com.
authors.forename: Rajpal S
authors.initials: RS
authors.lastname: Kashyap
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002648:Child; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D059425:Interferon-gamma Release Tests / Q000379:methods*; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D044382:Population Groups; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10
keywords: Cytokines; LTBI; QFT; TST