Bibliographic Details
| Title: |
A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis |
| Authors: |
Nika Zielinski, Dragos Baiceanu, Antonela Dragomir, Jan Heyckendorf, Elmira Ibraim, Niklas Köhler, Christoph Leschczyk, Cristina Popa, Andrea Rachow, Jens Sachsenweger, Patricia Carballo, Dagmar Schaub, Hajo Zeeb, Begna Tulu, Andrew DiNardo, Christoph Lange, Maja Reimann |
| Source: |
Pathogens and Immunity, Vol 9, Iss 2 (2024) |
| Publisher Information: |
Case Western Reserve University, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Pathology
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
adverse events, linezolid, neurotoxicity, precision medicine, SBSN, tuberculosis, Pathology, RB1-214, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Background: Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. Objective: We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Methods: Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. Results: A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 – 0.84). Conclusions: We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2469-2964 |
| Relation: |
https://www.paijournal.com/index.php/paijournal/article/view/705; https://doaj.org/toc/2469-2964 |
| DOI: |
10.20411/pai.v9i2.705 |
| Access URL: |
https://doaj.org/article/365a43413a324b05ac60e987d51979d9 |
| Accession Number: |
edsdoj.365a43413a324b05ac60e987d51979d9 |
| Database: |
Directory of Open Access Journals |
