Increased Production of the Soluble Tumor‐Associated Antigens CA19‐9, CA125, and CA15‐3 in Rheumatoid Arthritis

Abstract

Some tumor-associated antigens (TAAs) are expressed on inflammatory cells. We previously detected carcinoembryonic antigen (CEA; CD66) in the rheumatoid (RA) synovium. The production of CEA, CA19-9, CA125, and CA15.3, may be increased in patients with RA, scleroderma, lupus, and Sjögren's syndrome (SS). Some of these TAAs contain sialylated carbohydrate motifs and they are involved in tumor-associated cell adhesion and metastasis. We assessed levels of TAAs in the sera of RA patients and healthy subjects. Serum TAA levels were correlated with disease markers including serum rheumatoid factor (RF), C-reactive protein (CRP), and anti-CCP antibody levels, DAS28, age disease duration. TAAs including CEA, CA15-3, CA72-4, CA125, and CA19-9, and neuron-specific enolase (NSE) were assessed by immunoassay in the sera of 75 patients with RA and 50 age- and sex-matched healthy controls. Normal upper limits for these TAAs were 3.4 microg/L, 25 kU/L, 6.9 kU/L, 35 kU/L, 34 kU/L, and 16.3 microg/L, respectively. There were significantly more RA patients showing abnormally high levels of CA125 (10.8% versus 7.1%), CA19-9 (8.1% versus 0%), and CA15-3 (17.6% versus 14.3%) in comparison to controls (P < 0.05). The mean absolute serum levels of CA125 (23.9 +/- 1.8 versus 16.8 +/- 2.2 kU/L) and CA19-9 (14.2 +/- 1.2 versus 10.5 +/- 1.6 kU/L) were also significantly higher in RA compared to controls (P < 0.05). Among RA patients, serum CEA showed significant correlation with RF (r = 0.270; P < 0.05). None of the assessed TAAs showed any correlation with CRP, anti-CCP, DAS28, age or disease duration. The concentration of some TAAs may be elevated in the sera of patients with established RA in comparison to healthy subjects. CEA, CA19-9, CA125, and CA15-3 contain carbohydrate motifs and thus they may be involved in synovitis-associated adhesive events. Furthermore, some TAAs, such as CEA, may also correlate with prognostic factors, such as serum RF levels.

Serum Tumor Marker Levels in Rheumatoid Arthritis

“…In our findings, CEA levels have been found to be correlated with smoking history and serum RF levels however a correlation between disease activity score and CEA was not present. This finding is in accordance with another study also evaluating the level of serum tumor markers in RA patients in which disease activity was measured by DAS28 however in two other studies which also reported elevated CEA levels in RA patients, a correlation between RF and CEA levels were not found (11)(12)(13). Of interest there are a few studies in the literature that suggest CEA itself by binding to monocytes can trigger increased secretion of proinflammatuary cytokines such as tumor necrosis factor alfa, interleukin 1 beta and interleukin 6.…”

“…It is expressed on the cell surface and is responsible for cell adhesion to neighboring tissues (16 found that CA125 levels were significantly elevated in the patient group. In our study group CA 125 levels were found to be significantly higher in RA patients (11,12). Carbohydrate antigen 19-9 (CA 19-9) is a tumor associated oligosaccharide oncofetal antigen which is closely related to the sialylated Lewis blood group antigen (sLea).…”

Increased CA 19-9 level in patients without malignant disease

“…Our finding that an increased ESR was associated with an increased CA 19-9 concentrations further supports this idea. Furthermore, CA 19-9 along with other tumor markers was recently proposed as an adhesion molecule in synovial inflammation (23).…”

Diagnostic value of CA 19-9 in pregnancies complicated by spinal neural tube defects: a preliminary study

“…Carbohydrate antigen , also called sialylated Lewis antigen, is synthesized by normal human pancreatic and biliary ductal cells and by gastric, colon, endometrial, and salivary excretory epithelial tissues [7,8]. CA 19-9 is commonly used as a tumor marker for certain epithelial-type gastrointestinal cancers, particularly pancreatic.…”