Researchers Identify Biomarker that Heralds Poor Outcomes in TB Patients

By Colter Billings & Molly Bowen

November 8, 2021—Dr. Akshay Gupte, Instructor of Medicine in Infectious Diseases, and colleagues conducted a multi-site study with research partners in India and South Africa, and discovered that biomarker IL-6 forecasts poor clinical outcomes for patients with tuberculosis (TB). IL-6 is a promising marker that is gaining attention in disease research. It’s currently being studied for its predictive value for poor outcomes among COVID-19 patients. 

The study was conducted in 3 phases: the first “discovery” phase focused on patients enrolled in the Cohort for Tuberculosis Research by the Indo-US Medical Partnership (CTRIUMPH) in Pune and Chennai, India, where researchers looked at 20 biomarkers for their predictive value for poor treatment outcomes. The researchers found three markers that signaled the persistence of inflammation—IL-6, IL-13, and INFγ—were predictive of poor treatment outcomes in TB. The next “internal validation” phase in a different group of patients at the Byramjee Jeejeebhoy Government Medical College (BJGMC) in Pune, India, further refined the study by ruling out 2 markers and narrowing down the focus to IL-6. The third “external validation” phase expanded the study to a different cohort in Chennai, India, mostly comprising diabetic TB patients, and another one in South Africa, predominantly comprising HIV coinfected TB patients. With this third phase, IL-6 was validated as the strongest marker for predicting TB treatment failure, disease recurrence, and death. 

Researchers found consistent results across research sites, despite differences in study design, population, testing labs, and underlying comorbidities—like HIV in the South Africa cohort and diabetes in the Chennai cohort. Additionally, severity of symptoms had no impact; the study found that IL-6 predicts poor treatment outcomes among patients with severe, moderate, and mild TB symptoms. 

“We can tell which patients are at higher risk by looking for this marker,” Gupte said. “Adding IL-6 to clinical assessments increased the predictability for poor treatment outcomes by 15 percent over conventional assessments of chest x-rays, weight loss, and sputum tests, which is significant, and points to a need to include IL-6 in TB clinical screenings.” 
The study was conducted under the Regional Prospective Observational Research for Tuberculosis (RePORT) India Consortium, which represents India’s country-level participation in RePORT International, a global consortium focused on TB research. Other participating countries are Brazil, China, Indonesia, Philippines, and South Africa.

 “While previous studies have shown a non-specific correlation between IL-6 concentrations and TB, very few have made a connection between the marker and TB treatment outcomes,” said Dr. Amita Gupta, senior author on the study, Co-chair of RePORT India, and member of the RePORT International Executive Committee Leadership Group. “The RePORT Consortium is moving the needle on TB treatment through studies such as this.” 

Published Findings:
Gupte AN, Kumar P, Araújo-Pereira M, Kulkarni V, Paradkar M, Pradhan N, Menon P, Chandrasekaran PD, Hanna LE, Yogendra Shivakumar SVB, Rockwood N, Du Bruyn E, Karyakarte R, Gaikwad S, Bollinger R, Golub J, Gupte N, Viswanathan V, Wilkinson RJ, Mave V, Babu S, Kornfeld H, Andrade BB, Gupta A. Baseline IL-6 is a biomarker for unfavorable tuberculosis treatment outcomes: a multi-site discovery and validation study. Eur Respir J. 2021 Oct 28:2100905. doi: 10.1183/13993003.00905-2021. Epub ahead of print. PMID: 34711538.