Search bioRxiv⌕ Search

Biology subjects

Albert-Vega, C.

Publications and source records attributed to Albert-Vega, C..

2 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↗
bioRxiv2026

Functional alterations of immune gene expression in ICU and non-ICU patients with Legionnaires' disease, a prospective observational study

Legionnaires disease (LD), a pneumonia caused by Legionella pneumophila intracellular bacterium, leads to intensive care unit (ICU) admission in 20-40% of cases. While these ICU-LD patients display severe lung injury or septic shock, their functional immune response remains poorly understood. The present study aimed, through a large immune gene expression assessment, to improve the understanding of immune cell functionality after whole blood LPS ex vivo stimulation in ICU-LD patients compared with non-ICU. Both ICU and non-ICU-LD displayed altered gene expression indicating that both patients immune cells are less able to respond to the LPS ex vivo stimulus than a healthy population. ICU-LD patients had 1.6-fold greater number of less-expressed genes (35/93 vs 22/93, p=0.039), and lower Log2(FC) of these genes (median [IQR]: -1.9 [-2.6;-1.5] vs -1.2 [-1.7;-0.9], p=0.0011) than non-ICU-LD. Seven genes were significantly less expressed by ICU-LD patients (IRF7, MX1, NFKBI2, NFKBIA, RELB, SRC, TIM3; p-value range: 0.029-0.0080). Top five gene ontology biological processes, subcellular localisations, and reactome pathways (STRING database) uniquely enriched in ICU-LD-patients and related less-expressed genes were cellular response to LPS (CCL2, NFKBIA, IRAK2, TIM3, SRC, NFKB1), regulation of IFN-{beta} production (IRF7, RIG1, OAS2, RELB), I-{kappa}B/NF-{kappa}B complex (NFKBIA, NFKB1, NFKB2), IFN regulatory factor complex (RIG1, IRF7), and TRAF6-mediated NF-{kappa}B activation pathway (NFKBIA, NFKB1, NFKB2, RIG1). Immune gene expression alterations in LD after LPS stimulation were found herein, with more pronounced alterations in ICU-LD patients. A reduced expression of key genes and pathways involved in controlling Legionella proliferation in ICU-LD patients may contribute to increased disease severity.

immunology↗