Transcriptional and cytokine signatures of Mycobacterium abscessus complex pulmonary disease during disease progression and treatment.

Background: 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. 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.

Methodology/principal findings: To address the gaps in clinically relevant indicators, we profiled whole blood transcriptome and 45 plasma proteins of MABC-PD patients across different disease and treatment phases. Whole blood bulk RNA-sequencing revealed that MABC-PD patients with progressive disease exhibited elevated expression of genes related to innate immune and inflammatory responses, with reduced abundance of genes associated with peripheral T and NK cells. Among the 45 plasma cytokines and chemokines profiled, plasma levels of TNFSF10 were significantly reduced, while IFNγ, interleukin-17F (IL17F) and IL17C were elevated in patients with disease progression, despite the reduced abundance of peripheral T and NK cell-associated genes, suggesting recruitment of activated T cells to infection sites in the lungs during disease progression. Receiver operating characteristic (ROC) curve analysis of IFNγ and IL17F demonstrated strong predictive performance for differentiating patients with disease progression from healthy controls, with AUCs of 0.946 (95% CI 0.829-1.000) and 0.875 (95% CI 0.6699-1), respectively.

Conclusions: These findings provide insights into the immune profiles of MABC-PD patients during disease progression and suggest that T cell-associated cytokines, such as IFNγ and IL17F, could serve as useful biomarkers for identifying those under watchful waiting or post-treatment who are at risk of disease progression, thereby aiding in more timely and targeted therapeutic interventions.