# Single and Combined Serum Proteins Expressed in TB Infection are Candidates for Point-of-care Diagnostic Testing of Active TB Patients in Lambaréné, Gabon

## TL;DR

This study identifies specific serum proteins that could be used for quick and accurate diagnosis of active tuberculosis in remote areas.

## Contribution

The study confirms single and combined serum proteins as potential biomarkers for point-of-care TB diagnosis.

## Key findings

- Six proteins were differentially expressed in TB compared to pneumonia patients.
- Two single proteins and three-protein combinations showed ≥70% diagnostic performance.
- Three-protein combinations achieved 81% accuracy after cross-validation.

## Abstract

Point-of-care testing using nonsputum samples like serum or plasma proteins can improve tuberculosis (TB) patients access to a definitive diagnosis, especially in resource-constrained and remote areas. Recently, approximately 400 proteins were identified as playing a role in the pathogenesis of TB, offering a translational clinical research repository for TB. In a previous manuscript, we proved the potential use of these proteins for point-of-care testing for active TB diagnosis. The present work aims to confirm the performance of single and combination proteins to select the best candidate biomarkers for further development as a diagnostic testing tool for active TB.

Seventy-four participants were assessed on the diagnostic performance of 17 single proteins and combinations of 2 to 4 proteins to diagnose active TB. The selection criteria included differential expression of the proteins between active TB and community-acquired pneumonia (CAP) and a performance rate ≥70% for active TB.

SULT4A1, WASPF3, SPTLC1, FAM107B, SORCS2, and CYTOb561 were differentially expressed in TB compared to CAP patients. Two single proteins, SULT4A1 and WASPF3, performed ≥70% to discriminate active TB from CAP patients. The diagnostic performance of 3 protein-based combinations of active TB was 81% after leave-one-out cross-validation.

Single proteins and 3 protein-based combinations are candidate biomarkers for diagnosing active TB disease. A large and prospective study will confirm their performance as complementary diagnostic tools to rapid diagnostic methods for detecting active TB.