ADAMTS4 and Airway Remodeling in Human Asthma: A New Therapeutic Frontier

Abstract: Chronic airway inflammation involves complex immune dysregulation and structural remodeling of the lung tissue. While our previous work identified a pivotal role for ADAMTS4 in the immunopathology of acute infection-induced lung inflammation, its contribution to chronic pulmonary inflammation in humans remains unexplored. Aims and objectives: We aimed to investigate the role of ADAMTS4 in chronic airway inflammation in individuals diagnosed with asthma. Methods: Plasma samples were collected from individuals with COVID-like symptoms or known SARS-CoV-2 exposure, following informed consent. Clinical data spanning 30 days pre- and post-enrollment were recorded. Participants underwent PCR testing, and those with negative results and a confirmed asthma diagnosis were included. ADAMTS4 levels in plasma were measured by ELISA. Lung specimens from five asthmatic and five non-asthmatic individuals were pathologist-verified. Tissue sections underwent H&E, Alcian Blue, PAS staining, and immunofluorescence for versican and α-smooth muscle actin. Images were captured for analysis. Results: ADAMTS4 levels were significantly elevated in the blood of asthmatic patients compared to healthy controls. Lung sections from asthmatic individuals also showed marked upregulation of ADAMTS4. Additionally, immunofluorescence staining revealed substantially increased versican expression in asthmatic lung tissues, which was absent in non-asthmatic samples. Conclusion: Our findings demonstrate for the first time that ADAMTS4 is highly upregulated in human lungs of asthma patients. This upregulation is spatially colocalized in the areas of versican accumulation, suggesting a key role for the enzyme in human asthma pathogenesis.