Cytokine Signatures and Clinical Characteristics Associated with Conversion and Reversion of IGRA-based TB Screening among Healthcare Workers in North-Central Nigeria: A Pilot Study

Background The substantial burden of subclinical Mycobacterium tuberculosis (Mtb) infection continues to be a key reservoir and driver of the tuberculosis (TB) epidemic, particularly in countries with high TB and HIV prevalence. Fluctuations in IFN-γ release assay (IGRA) status (conversion and reversion) undermine precise estimates of the subclinical TB reservoir and hinder efforts to control transmission and progression to active disease. In this study, we assessed differences in the level of pro-inflammatory and anti-inflammatory cytokines between converters and non-converters, as well as between reverters and non-reverters. Methods We retrieved stored unstimulated plasma samples of 72 participants (Healthcare Workers) from selected healthcare facilities in North-central Nigeria. Samples were categorized into four groups based on two longitudinal IGRA (QFT-Plus) results at month 0 (M0) and month 18 (M18): non-converters (M0- and M18-); converters (M0- and M18+), non-reverters (M0 + and M18+); and reverters (M0 + and M18-). The samples were analyzed for the concentrations of 18 cytokines using the Luminex® technology platform. Median differences in the concentrations of cytokine between converters and non-converters, reverters and non reverters were then assessed using the Mann-Whitney test. Results We observed that the median level of three plasma cytokines (MIF ( p -value = 0.067), IL2 ( p -value = 0.055), and IL5 ( p -value = 0.055)) were significantly different between converters and non-converters, while the median level of two plasma cytokines (IL1β (0.0547) and IL13 (0.0758)) were significantly different between reverters and non-reverters. Conclusion Although preliminary, this study provides foundational findings linking the potential role of cytokines as biomarkers that may be associated with IGRA conversion and reversion. Future studies will look to establish the utility of these cytokines as biomarkers for subclinical TB.