Pneumologie 2015; 69 - P462
DOI: 10.1055/s-0035-1544879

Molecular heterogeneity of mucin as a potential biomarker for inflammatory airway disorders: identification of detection reagents

T Krause 1, K Ramaker 1, H Sinnecker 1, A Frey 1
  • 1Division of Mucosal Immunology & Diagnostics, Research Center Borstel

Evidence accumulates that airway mucins harbour disease-related alterations in their composition and glycosylation. For cystic fibrosis patients a correlation between the severity of airway infections and an increase in mucin sialylation was described. A similar change in glycosylation was observed upon the induction of asthma in experimental animals. In case of COPD the ratio of the two major airway mucins MUC5AC and MUC5B was reported to differ from that in healthy individuals. This opens the possibility to diagnose and monitor inflammatory airway disorders based on the composition and glycosylation of the mucin from patient samples.

In order to address this diagnostic avenue it is important to capture the mucin from the samples in a reliable way with little or no inter-patient variability. To identify appropriate mucin-specific reagents suited for this task, we tested anti-mucin antibodies on mucin-content-standardized human bronchoalveolar lavage samples and cell culture supernatants in immunoblot assays. We started out with all commercially available antibodies against Muc5AC as one of the major secretory airway mucins, except for the ones with known binding specificity to glycostructures. Our results show considerable inter-patient and inter-antibody variability in mucin recognition for all of the antibodies and samples tested which renders antibody-based mucin expression studies on human samples error prone. This should be kept in mind when interpreting immuno- and histochemical mucin expression data in clinical studies. The reason for these abberrancies is not clear. We assume that virtually all anti-mucin antibodies raised so far are directed against epitopes specific for the parent immunogen only, in most instances probably recognizing the highly variable carbohydrate portion of the mucin. In order to obtain universally applicable mucin detection reagents we are trying to identify conserved, antibody-accessible epitopes on human airway mucins.