Carcinoembryonic antigen (CEA) is a useful screening biomarker for inherited glycosylphosphatidylinositol deficiencies.

Abstract

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5/CEA) is a glycosylphosphatidylinositol (GPI)-anchored protein used as a serum tumor marker. Because GPI-anchored proteins may be released into blood in inherited GPI deficiencies (IGDs), we assessed whether serum CEA is a biomarker to support the diagnosis of IGDs. METHODS: Serum CEA concentrations were measured in patients with IGDs and compared with controls. To examine release mechanisms, GPI-anchor-biosynthesis-deficient cells were transfected with CEACAM5 and CEA in conditioned media was quantified. Secreted fragments were analyzed by mass spectrometry to determine cleavage sites. RESULTS: Serum CEA concentrations were significantly elevated in patients with IGDs compared with controls. Following CEACAM5 transfection, cells lacking several GPI-pathway genes secreted large amounts of CEA. Mass spectrometric analysis identified multiple cleavage sites in the secreted CEA fragments, including four corresponding to the ω-sites for GPI anchoring and additional sites consistent with protease-mediated cleavage. CONCLUSIONS: CEA is expressed on the apical surface of epithelial cells of intestine, stomach, and bronchus, and under normal conditions it does not enter the bloodstream even if released from the cell surface. Therefore, CEA levels are typically low in healthy children, reducing the likelihood of false-positive results compared with alkaline phosphatase. Elevated CEA was observed across most IGD subtypes. In combination with reduced granulocyte CD16 expression, serum CEA may serve as a complementary and robust biomarker for detecting inherited GPI deficiencies and may facilitate screening strategies.

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