Biology subjects

Musvosvi, M.

Publications and source records attributed to Musvosvi, M..

3 recordsLinked to original sources

bioRxiv2026

Integration of immunomonitoring assays with PET/CT in TB patients identifies on-treatment biomarkers

Tuberculosis (TB) continues to pose a significant global public health challenge with substantial patient morbidity and mortality. Current TB patient biomarkers lack sufficient resolution to inform treatment response and patient stratification. This necessitates the development of sensitive and reliable host biomarkers. We previously demonstrated the efficacy of TruCulture whole blood stimulation for differentiating asymptomatic TB from active pulmonary TB disease patients in endemic regions. Our systems immunology study expands upon this previous work by evaluating the potential of TruCulture to monitor longitudinal responses to TB treatment in patients from the Predict-TB trial before, during, and after 6 months of antibiotic therapy. We stimulated whole blood from TB patients (n=40) using TruCulture under four conditions (Null, Mycobacterium tuberculosis-antigen, LPS, and IL-1{beta}) at baseline (week 0), during treatment (weeks 16 and 24), and one-year follow-up post- treatment (week 72). 20/25 measured cytokines exhibited significant changes throughout treatment, with several continuing to evolve during post-therapy follow-up. Machine learning based analysis identified Mtb-Ag-induced IL-1RA (AUC = 0.90, 0.92, 0.95 at weeks 16, 24, 72) and LPS-induced NLRP3 (AUC = 0.94 at week 16) as the best protein and transcriptional biomarkers for distinguishing treated from untreated patients, strongly implicating the inflammasome response. Combining these results with the extent of lung disease assessed by FDG PET/CT scans, we showed direct disease relevance for these blood-based biomarkers. The identified biomarker profiles hold promise for improving TB patient care through early prediction of treatment responses, real-time therapy monitoring, and informed development of host-directed therapeutic strategies for clinical decision-making. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=146 HEIGHT=200 SRC="FIGDIR/small/723467v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@15ae804org.highwire.dtl.DTLVardef@136939forg.highwire.dtl.DTLVardef@15ac58org.highwire.dtl.DTLVardef@e5d8f0_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Predict-TB clinical study overview and summary of TB-specific biomarkers identified from TruCulture whole blood stimulation system. C_FIG

immunology↗

bioRxiv2020

Tuberculosis alters immune-metabolic pathways resulting in perturbed IL-1 responses

Tuberculosis (TB) remains a major public health problem with host-directed therapeutics offering potential as novel treatment strategies. However, their successful development still requires a comprehensive understanding of how Mycobacterium tuberculosis (M.tb) infection impacts immune responses. To address this challenge, we applied standardised immunomonitoring tools to compare TB antigen, BCG and IL-1{beta} induced immune responses between individuals with latent M.tb infection (LTBI) and active TB disease, at diagnosis and after cure. This revealed distinct responses between TB and LTBI groups at transcriptomic, proteomic and metabolomic levels. At baseline, we identified pregnane steroids and the PPAR{gamma} pathway as new immune-metabolic drivers of elevated plasma IL-1ra in TB. We also observed dysregulated induced IL-1 responses after BCG stimulation in TB patients. Elevated IL-1 antagonist responses were explained by upstream differences in TNF responses, while for IL-1 agonists it was due to downstream differences in granzyme mediated cleavage. Finally, the immune response to IL-1{beta} driven signalling was also dramatically perturbed in TB disease but was completely restored after successful antibiotic treatment. This systems immunology approach improves our knowledge of how immune responses are altered during TB disease, and may support design of improved diagnostic, prophylactic and therapeutic tools.

immunology↗

bioRxiv2019

Immune profiling in M. tuberculosis infection enables stratification of patients with active disease

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and is a major public health problem with an estimated 1.7 billion persons infected worldwide. Clinical challenges in TB include the lack of a blood-based test for active disease, and the absence of prognostic biomarkers for early treatment response. Current blood based tests, such as QuantiFERON-TB Gold (QFT), are based on an IFN{gamma} readout following Mtb antigen stimulation. However, they do not distinguish active TB disease from asymptomatic Mtb infection. We hypothesized that the use of TruCulture, an improved immunomonitoring method for whole blood collection and immune stimulation, could improve the discrimination of active disease from latent Mtb infection. To test our hypothesis, we stimulated whole blood from active TB patients (before and after successful treatment), comparing them to asymptomatic latently infected individuals. Mtb-specific antigens (ESAT-6, CFP-10, TB7.7) and live bacillus Calmette-Guerin (BCG) were used for TruCulture stimulation conditions, with direct comparison to QFT. Protein analyses were performed on the culture supernatants using ELISA and Luminex multi-analyte profiling. TruCulture showed an ability to discriminate active TB cases from latent controls (p < 0.0001, AUC = 0.81, 95% CI: 0.69-0.93) as compared to QFT (p = 0.47 AUC = 0.56, 95% CI: 0.40-0.72), based on an IFN{gamma} readout after Mtb antigen stimulation. The stratification of the two groups could be further improved by using the Mtb Ag/BCG IFN{gamma} ratio response (p < 0.0001, AUC = 0.918, 95% CI: 0.84-0.98). We also identified additional cytokines that distinguished latent infection from TB disease; and show that the primary differences between the TruCulture and QFT systems were a result of higher levels of non-specific innate immune activation in QFT tubes, due to the lack of a buffering solution in the latter. We conclude that TruCulture offers a next-generation solution for whole blood stimulation and immunomonitoring with the possibility to discriminate active and latently infected persons.

immunology↗