# Precision immunoprofiling to reveal diagnostic biomarkers of latent TB infection

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $722,295

## Abstract

PROJECT SUMMARY
 Tuberculosis (TB) is among the leading causes of mortality worldwide with an estimated 2 billion individuals
currently infected. Latent tuberculosis infection (LTBI) is the most common form of TB infection affecting 13
million Americans. While many with LTBI remain asymptomatic, an estimated 10% of immunocompetent patients
with LTBI will reactivate to active TB, and will become infectious. LTBI is treatable with a prolonged antibiotic
treatment; however, potential side effects motivate the development of new diagnostic approaches that can
identify with high specificity patients at the highest risk of reactivation, for who therapy would be most beneficial.
 The tuberculin skin test (TST) and interferon-γ release assays (IGRAs) are commonly used for TB and LTBI
screening. Both tests provide good measures of TB exposure; however, neither is effective at diagnosing LTBI
(positive predictive values <5%). Moreover, neither provide any prognostic stratification based upon reactivation
risk. Both the TST and IGRAs probe immunological memory to TB-related antigen challenges and we
hypothesize that a more nuanced and personalized approach to monitoring immune responses to both TB-
specific and non-specific antigens might reveal new approaches to LTBI diagnosis and patient stratification.
 Enabling a new, individualized approach to LTBI diagnostics, we propose to combine high throughput,
multiplexed inflammatory biomarker detection strategies and powerful bioinformatics tools that allow for the
identification of previously obscured multi-marker diagnostic signatures of LTBI status and reactivation risk.
Silicon photonic microring resonators are an enabling technology for biomarker analysis due to their intrinsic
scalability and multiplexing capabilities. Applied to the detection of cytokine panels, this technology supports the
rapid immune profiling of individual samples under both TB-specific and non-specific antigen stimulation
conditions. Machine learning algorithms will be utilized to analyze the resulting dense data streams to facilitate
selection of key diagnostic signatures forming the basis for predictive model development and deployment. This
powerful analytical combination is supplemented by deep expertise in clinical diagnosis and treatment of TB and
LTBI, and an enabling collaboration and connection to subjects from an international location with high TB burden
and exposure in a healthcare worker population subjected to regularly-scheduled and repeated LTBI screening.
 The resulting diagnostic workflow and machine learning feature selection approaches will reveal multiplexed
biomarker signatures that have strong positive predictive correlation with LTBI status (+ or -). This approach will also
further stratify LTBI+ subjects on the basis of reactivation potential, thus providing a fundamentally new approach to
identifying subjects that are most likely to benefit from therapeutic intervention. The end result of this project will ...

## Key facts

- **NIH application ID:** 10006790
- **Project number:** 5R01AI141591-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ryan C Bailey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $722,295
- **Award type:** 5
- **Project period:** 2019-09-05 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006790

## Citation

> US National Institutes of Health, RePORTER application 10006790, Precision immunoprofiling to reveal diagnostic biomarkers of latent TB infection (5R01AI141591-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10006790. Licensed CC0.

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