Photo Credit: iStock.com/Rasi Bhadramani

In Mycobacterium abscessus complex pulmonary disease, elevated levels of IFN-γ and IL-17F may signal higher risk for disease progression, researchers reported.

Elevated levels of interferon-γ (IFN-γ) and interleukin-17F (IL-17F) may indicate an increased risk for disease progression and the need for timely intervention in patients with Mycobacterium abscessus complex pulmonary disease (MABC-PD), according to study findings published online in PLOS Neglected Tropical Diseases.

“Mycobacterium abscessus complex pulmonary disease (MABC-PD) is a chronic and often relapsing disease with considerable morbidity, especially among individuals with other chronic pulmonary conditions,” wrote corresponding author Dorothy Hui Lin Ng, MBBS, PhD, of Singapore General Hospital, and coauthors in an uncorrected proof on the journal website. “A major clinical challenge lies in distinguishing infection-related symptoms from underlying lung disease and identifying reliable prognosticators to guide treatment decisions and monitoring therapeutic response.”

Analysis Addresses the Challenge

To address this challenge, researchers evaluated the whole blood transcriptome and measured 45 plasma proteins across different disease stages and treatment phases. The study cohort included four patients with MABC-PD receiving intensive phase treatment, four undergoing continuation phase therapy, seven in remission after treatment, seven patients managed with watchful waiting, and eight healthy control participants.

Study analysis of whole blood bulk RNA sequencing data revealed that patients experiencing progressive MABC-PD showed an elevated expression of genes associated with innate immune responses and inflammatory pathways. In contrast, these patients exhibited a reduction in the abundance of genes linked to peripheral T cells and natural killer (NK) cells.

Despite the diminished presence of these immune cell markers, patients with disease progression demonstrated significantly reduced plasma levels of TNFSF10 (also known as tumor necrosis factor–related apoptosis-inducing ligand) and concurrently displayed elevated concentrations of IFN-γ, IL-17F, and IL-17C.

The researchers wrote that “elevated levels of IFN-γ, IL17-F, and IL-17C—cytokines produced by activated T cells—argue against T cell exhaustion as a primary explanation. Instead, these findings suggest robust T cell activation and potential relocalization to the infection sites in the lungs.”

Receiver operating curve analyses further highlighted the clinical utility of these biomarkers. Interferon-γ and IL-17F showed strong predictive performance, with area under the curve (AUC) values of 0.9464 and 0.875, respectively. In contrast, IL-17C’s AUC value of 0.7857 did not reach statistical significance.

Beneficial Biomarkers

“Collectively, our findings suggest that IFN-γ and IL-17F could potentially serve as biomarkers for identifying MABC-PD patients who may benefit from treatment and differentiate them from those who can be managed with continued watchful waiting,” the authors concluded.