Inflammatory immune profiles associated with disease severity in pulmonary tuberculosis patients with moderate to severe clinical TB or anemia.

Background

Immune control of

Methods

Plasma samples were obtained from n=107 patients with active pulmonary TB at the time of diagnosis and after start of standard chemotherapy. A composite clinical TB symptoms score, blood hemoglobin status and chest X-ray imaging were used to sub-group TB patients into 1.) mild and moderate-severe clinical TB, 2.) anemic and non-anemic TB, or 3.) limited and extensive lung involvement. Plasma levels of biomarkers associated with inflammation pathways were assessed using a Bio-Plex Magpix 37-multiplex assay. In parallel, Th1/Th2 cytokines were quantified with a 27-multiplex in matched plasma and cell culture supernatants from whole blood stimulated with

Results

Clinical TB disease severity correlated with low blood hemoglobin levels and anemia but not with radiological findings in this study cohort. Multiplex protein analyses revealed that distinct clusters of inflammation markers and cytokines separated the different TB disease sub-groups with variable efficacy. Several top-ranked markers overlapped, while other markers were unique with regards to their importance to differentiate the TB disease severity groups. A distinct immune response profile defined by elevated levels of BAFF, LIGHT, sTNF-R1 and 2, IP-10, osteopontin, chitinase-3-like protein 1, and IFNα2 and IL-8, were most effective in separating TB patients with different clinical disease severity and were also promising candidates for treatment monitoring. TB patients with mild disease displayed immune polarization towards mixed Th1/Th2 responses, while pro-inflammatory and B cell stimulating cytokines as well as immunomodulatory mediators predominated in moderate-severe TB disease and anemia of TB.

Conclusions

Our data demonstrated that clinical disease severity in TB is associated with anemia and distinct inflammatory immune profiles. These results contribute to the understanding of immunopathology in pulmonary TB and define top-ranked inflammatory mediators as biomarkers of disease severity and treatment prognosis.

Informations de copyright

Copyright © 2023 Ashenafi, Loreti, Bekele, Aseffa, Amogne, Kassa, Aderaye and Brighenti.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.