Acute Phase Proteins Are Baseline Predictors of Tuberculosis Treatment Failure.

Nathella Pavan Kumar,Kannan Thiruvengadam,Hardy Kornfeld,Kadar Moideen,Arul Nancy,Syed Hissar,Subash Babu,Shanmugam Sivakumar,Vijay Viswanathan

doi:10.3389/fimmu.2021.731878

Abstract

Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive individuals with drug-sensitive PTB, were treated with standard anti-tuberculosis treatment and classified as having treatment failure or microbiological cure. The plasma levels of acute phase proteins were assessed at baseline (pre-treatment). Baseline levels of C-reactive protein (CRP), alpha-2 macroglobulin (a2M), Haptoglobin and serum amyloid P (SAP) were significantly higher in treatment failure compared to cured individuals. ROC curve analysis demonstrated the utility of these individual markers in discriminating treatment failure from cure. Finally, combined ROC analysis revealed high sensitivity and specificity of 3 marker signatures comprising of CRP, a2M and SAP in distinguishing treatment failure from cured individuals with a sensitivity of 100%, specificity of 100% and area under the curve of 1. Therefore, acute phase proteins are very accurate baseline predictors of PTB treatment failure. If validated in larger cohorts, these markers hold promise for a rapid prognostic testing for adverse treatment outcomes in PTB.

Highlights

Systemic inflammation is a characteristic hallmark of pulmonary tuberculosis (PTB) [1,2,3]
Systemic inflammation is typically characterized by elevations in the levels of acute phase proteins, including C-reactive protein (CRP), apha-2 macroglobulin (a2M), haptoglobin (Hp) and serum amyloid P (SAP) [4,5,6,7]
We have previously reported that plasma chemokine signatures [16], as well as Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) [17] can be used as novel biomarkers for predicting adverse treatment outcomes like failure, relapse, and death in individuals with PTB

Summary

INTRODUCTION

Systemic inflammation is a characteristic hallmark of pulmonary tuberculosis (PTB) [1,2,3]. Several studies have associated increased circulating levels of these acute phase proteins with PTB and CRP is often used a point-of-care test to aid in the diagnosis of PTB [8,9,10,11,12,13]. Studies have reported that haptoglobin is clinically a relevant host biomarker for TB diagnosis and disease progression [14]. We hypothesized that TB treatment failures would be driven by heightened systemic inflammation at baseline. To test this hypothesis, we examined the baseline levels of acute phase proteins in a nested case-control study of TB treatment failure versus cure in a cohort of PTB individuals in Chennai, India. Our results show that acute phase proteins are baseline predictors of treatment failure

Ethics Statement

RESULTS

DISCUSSION