# Complement profiling for treatment outcomes in pulmonary TB

## TL;DR

This study explores how the complement system's activity at the start of treatment affects outcomes in pulmonary TB patients.

## Contribution

The study identifies specific complement components as potential early indicators of poor TB treatment outcomes.

## Key findings

- TB patients with poor outcomes had higher levels of C3, C3b, C4b, C5, C5a, and C1q compared to controls.
- Lower levels of Factor B and Factor H were observed in TB patients with poor outcomes.
- Early complement activation through the classical pathway is linked to adverse TB treatment outcomes.

## Abstract

The complement system plays a vital role in the immune response against tuberculosis (TB), aiding in the recognition and clearance of Mycobacterium tuberculosis. However, its imbalance can result in either insufficient immune activation or excessive inflammation, both of which may contribute to poor treatment outcomes.

This study investigates whether baseline complement profiles are associated with unfavorable treatment responses in pulmonary TB patients. Using the Magpix multiplex cytokine assay, plasma levels of complement components (C2, C3, C3b/iC3b, C4, C4b, C5, C5a, C1q, MBL) and regulatory proteins (Factor B, Factor D, Factor H, Factor I) were measured in TB patients with poor treatment outcomes (n=68) and disease-free controls (n=108).

At both baseline (pre-treatment) and month two of anti-TB therapy, cases had significantly elevated levels of C3, C3b, C4b, C5, C5a, and C1q, and reduced levels of Factor B and Factor H compared to controls. Regression modelling revealed that C3, C3b, C4b, C5, C5a and C1q were associated with increased risk of unfavorable outcomes in unadjusted and adjusted analyses in the study cohort.

These findings suggest that early and sustained complement activation, particularly through the classical pathway, is associated with adverse outcomes in TB. Complement dysregulation may thus serve as a potential prognostic marker for identifying individuals at risk of poor treatment response.