Elevated Levels of Serum Mucin-associated Antigen in Adult Patients with Cystic Fibrosis

Abstract

Previous studies using the CA 19-9 antibody have demonstrated that serum mucin levels in patients with cystic fibrosis (CF) are elevated and that the degree of elevation relates to the age of the patient and possibly to his or her clinical status. However, CA 19-9 only recognizes the mucin-associated blood group sialyl Le(a+) antigen, so mucin levels cannot be measured in patients without Lewis antigens. The present study used the 17B1 monoclonal antibody to measure serum mucin levels in normal subjects, and in patients with CF, patients with chronic obstructive pulmonary disease (COPD), and patients with lung transplants. Serum mucin levels were 25 ng/ml (+/- 1 SEM, n = 8) in normal subjects, 13,853 ng/ml (+/- 1,281, n = 25) in patients with CF, and 25.5 ng/ml (+/- 1.9, n = 17) in patients with COPD. Patients with CF who were sialyl Le(a-b-) also had elevated serum mucin levels (715 +/- 152, n = 2). Serum mucin levels of six lung transplant recipients with CF were elevated compared with those in normal subjects (4,621 +/- 765 ng/ml), but they were not different from serum mucin levels in six lung transplant recipients without CF (5,307 +/- 1.677 ng/ml). Preliminary characterization of the serum mucin antigen showed that: (1) in CF sera, the antigen is polydisperse and smaller than the antigen in normal sera; (2) the mucin antigen is distinct from ABO blood group antigens. Serum mucin levels may be a useful marker to follow a specific patient's response to therapy.

PARTITIONING LUNG AND PLASMA PROTEINS: CIRCULATING SURFACTANT PROTEINS AS BIOMARKERS OF ALVEOLOCAPILLARY PERMEABILITY‡

“…However, because airway infection and inflammation are common in chronic obstructive pulmonary diseases, such as bronchitis, asthma, bronchorrhoea and bronchopulmonary dysplasia, it is possible that permeability is increased in these patients. Perhaps consistent with increased inflammatory and protease activity and the fact that protein transport across the bronchial epithelium is usually accompanied by degradation, whereas proteins cross the alveolar epithelium largely intact, 46 serum mucin from cystic fibrosis 68 and ARDS 69 patients has a smaller M r than mucin found in normal subjects. Alternatively, because biosynthesis, processing and secretion of mucins is complex, the increased respiratory mucin in the sera of patients with respiratory disorders could be a consequence of an aberration in one or more of these steps, primarily or secondarily related to the disease process, rather than reflecting changes in permeability 70 .…”

“…In contrast with the distribution of Clara cells, these cells are located primarily in the higher airway rather than the bronchioles. Although elevated respiratory specific mucin antigens have been described in the circulation in a number of respiratory diseases, including cystic fibrosis, 65 interstitial pneumonia, pulmonary fibrosis, tuberculosis, 66 , 67 lung transplant 68 and ARDS, 69 the manner in which the peptides gain access is unclear.…”

“…Normally, native mucin is too large (154 to > 7000 kDa) and too negatively charged to breach the tight junctions of the negatively charged bronchocapillary epithelium 68 , 70 . However, because airway infection and inflammation are common in chronic obstructive pulmonary diseases, such as bronchitis, asthma, bronchorrhoea and bronchopulmonary dysplasia, it is possible that permeability is increased in these patients.…”

Infants and Young Children with Cystic Fibrosis Have High Levels of Serum Sialyl Lewisa Antigen

“…Second, in our 1989 study, we found the mean serum mucin level as detected with the CA 19-9 MAb to be significantly higher in 8 1 CF patients (adults and children) with Pseudomonas in their sputa than in six bronchiectatic non-CF adults who had Pseudomonas in their sputa. With the exception of similar serum mucin elevations in both CF and non-CF lung transplant patients (30), elevated serum mucin levels are associated with CF lung disease rather than with either purulent or dry non-CF lung diseases.…”

Serum CA 19?9 levels as a diagnostic marker in cystic fibrosis patients with borderline sweat tests

“…In another study, they demonstrated the CA 19-9 levels to be significantly higher in CF patients than in bronchiectatic non-CF patients; all patients of both groups had Pseudomonas in their sputum [15]. Robinson et al [16] found significantly higher serum mucin levels in CF patients than in patients with chronic obstructive pulmonary disease with a strong "bronchitic" component, who produced up to one-half a cup of sputum daily. Elevated serum mucin levels are associated with CF rather than with either purulent or dry non-CF lung disease [14].…”