Soluble isoforms of CEACAM1 containing the A2 domain: increased serum levels in patients with obstructive jaundice and differences in 3-fucosyl-N-acetyl-lactosamine moiety

CEACAM1 (biliary glycoprotein or CD66a) is a member of the carcinoembryonic antigen (CEA) subgroup of the CEA family. Eleven RNA isoforms derived from the splicing of a single CEACAM1 gene have been described. Some of the CEA CAM1 isoforms have been recognized by the CD66 antibodies in T and B lympho cytes, natural killer cells, granulocytes and epithelial cells in several h uman tissues. Although it is also present in soluble form in bile and serum , and elevated levels have been found in the serum of patients with liver d iseases, it is not known which isoforms are primarily involved. In order to learn more about the distribution and properties of particular CEACAM1 iso forms, we have prepared a monoclonal antibody specific for the A2 domain of CEACAM1, designated TEC-11. This antibody does not cross-react with other members of the CEA family. Immunoblotting analysis revealed that the TEC-11 epitope was present in all cell types expressing CEACAM1 containing the A2 domain [CEACAM1(A2)], including granulocytes (160 000 MW isoform) and sper m cells (140 000 MW isoform). A 115 000 MW isoform of CEACAM1(A2) was prese nt in human serum, bile, saliva and seminal fluid. Human bile, saliva and s eminal fluid also contained the 160 000 MW CEACAM1(A2) isoform. Significant ly higher serum levels of the 115 000 MW CEACAM1(A2) isoform were detected in patients with obstructive jaundice. The 160 000 MW isoform of CEACAM1(A2 ) in bile, but not a 115 000 MW isoform in serum and bile, carried the 3-fu cosyl-N-acetyl-lactosamine moiety. The combined data indicate that various isoforms of CEACAM1(A2) are present in different body fluids where they cou ld take part in different CEACAM1-mediated functions.