Airway mucins – suitable biomarkers to predict an upcoming exacerbation in COPD and asthma?

Mucins are large glycoproteins lining and protecting the epithelial airway surface. However, their amount, composition and glycosylation pattern can be affected by the airway environment including the inflammatory status of the lung. In COPD amount and ratio of the two most important airway mucins MUC5AC and MUC5B are altered compared to the healthy situation. Moreover, variations in the glycosylation pattern of airway mucins were observed in asthma animal models as well as in patients with cystic fibrosis, making mucin composition and characteristics potential biomarkers to detect and even predict upcoming, life threatening exacerbations in chronic inflammatory airway disorders.

To analyze whether distinct alterations of the mucin composition are representative for inflammatory airway processes like COPD and asthma, we purified mucins from bronchoalveolar lavage fluid (BALF) of healthy and airway-diseased individuals and subjected them to a comprehensive lectin-binding assay to screen for disease-specific glycosylation patterns. With this assay we are currently identifying combinations of lectins, corresponding to distinct glycostructures, characteristic for mucins from healthy, airway-diseased and exacerbated individuals.

Although very informative, the lectin-binding assay depends on laborious mucin pre-purification and cannot distinguish between different airway mucins. To make use of mucin alterations as potential biomarker in a more general, versatile test system, it is therefore essential to catch and analyze specific mucins from human samples donor- and disease-status independent and with little effort. Antibodies specifically targeting the protein backbone of the different mucins could be viable tools. However, commercially available antibodies against the major airway mucin MUC5AC are not able to detect equal amounts of protein in a patient- and disease-independent manner making them unsuitable for our purpose. In an attempt to change this, we are currently identifying epitopes within the protein backbone of MUC5AC consistently accessible for antibodies and thereby potential targets for universally reactive mucin capture reagents.