A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis

Area of Science:

• Pharmacogenomics
• Neuroscience
• Infectious Diseases

Background:

• Linezolid treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) frequently causes neuropathic adverse events.
• Some linezolid-associated neuropathies can be irreversible, necessitating predictive biomarkers.

Purpose of the Study:

• To identify and validate a host RNA-based biomarker predicting linezolid-associated neuropathy before MDR/RR-TB treatment.
• To identify genes and pathways linked to linezolid-associated neuropathy.

Main Methods:

• Prospective enrollment of adult patients initiating MDR/RR-TB treatment with linezolid across three German cohorts.
• Whole blood RNA transcriptomic analysis and clinical data collection.
• Biomarker identification using a random forest algorithm and validation in a fourth Romanian cohort.

Main Results:

• 46.2% of patients developed peripheral and/or optic neuropathies during linezolid treatment.
• Suprabasin (SBSN) expression was identified as a potential predictive biomarker.
• The biomarker algorithm showed moderate predictive performance (AUC 0.63) for grade ≥3 neuropathies in the validation cohort.

Conclusions:

• A potential clinical biomarker (SBSN) for predicting linezolid-associated neuropathies before MDR/RR-TB therapy initiation was identified and preliminarily validated.
• Further research with larger, diverse populations is needed to confirm the SBSN biomarker's utility.