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

Abstract

Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19-9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19-9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19-9 levels, but normal levels do not exclude cystic fibrosis.

Hepatobiliary complications of cystic fibrosis

“…Several potential markers of hepatic injury and inflammation have been shown to be elevated in CF patients with liver disease, including glutathione S-transferase B1 [37], high molecular mass alkaline phosphatase [38], and serum hyaluronic acid [39]. Other markers of liver and biliary inflammation, such as plasma transforming growth factor (TGF) B1 levels [40] or CA 19-9 [41], have not been as useful in distinguishing CF patients with liver disease. Recently, serum markers to detect liver fibrosis have been evaluated in several liver diseases, including CF.…”

Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis

“…Cytokine concentrations were also thoroughly analyzed in the bronchoalveolar lavage fluid (BALF) 9,18 and in sputum samples from CF patients 19 . Moreover, tumor markers, such as cancer antigens (CA) 125 and CA 19-9, were connected with Pseudomonas aeruginosa lung colonization and impaired lung function 20 , while CA 19-9 may discriminate cases with borderline sweat chloride M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 6 concentrations 21 . However, assessment of various biomarkers has been primarily considered within the scientific domain, rather than as part of routine CF laboratory diagnostics.…”

Screening strategy for gastrointestinal and hepatopancreatobiliary cancers in cystic fibrosis

“…Patients with CF have shown to experience non-specific elevations in serum CA-19-9 levels, with volumes up to 500 U/mL (reference range 0-37 U/mL)[ 55 - 58 ]. Some sources have linked increased serum CA-19-9 Levels with active CF-related liver disease[ 54 ] and pulmonary exacerbation[ 57 , 59 - 61 ]. CA-19-9 has a 20% false-positive rate as a screening test and the serum level may also be elevated with other conditions, including an increased production of sputum, diabetes, chronic kidney failure, and infections.…”