The reactivity of alpha-1-antitrypsin with Lens culinaris agglutinin and its usefulness in the diagnosis of neoplastic diseases of the liver

Abstract

Summary The reactivity of alpha-l-antitrypsin (AAT) with Lens culinaris agglutinin (LCA) was studied by crossed immuno-affinity electrophoresis of the sera of 246 subjects from 6 groups (acute virus hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma (HCC), carcinoma metastatic to the liver and normal controls). Two species of AAT (LCA-reactive and -nonreactive species) were detected on crossed immuno-affinity electrophoresis in a gel containing LCA. The percentages of LCA-reactive species of AAT in neoplastic diseases of the liver were significantly higher than those in benign liver diseases and normal controls. There was no correlation between the percentage of LCA-reactive species of AAT and serum AAT concentration in any group. Furthermore, in studying 15 pairs of serum samples before and after the subsequent development of HCC, the percentage of LCA-reactive species of AAT after HCC occurrence was significantly higher than that before, although there was no statistically significant difference between the serum AAT concentration before and after development of the disease. The latter 15 patients were all of the normal protease inhibitor phenotype (PiMM) and no change in phenotype was observed before and after the development of HCC. The results indicate that measurement of the reactivity of AAT with LCA can be a useful marker for the diagnosis of HCC and carcinoma metastatic to the liver, especially when serum concentrations of alpha-foetoprotein or other tumour markers are within the normal ranges.

Highly enhanced fucosylation of serum glycoproteins in patients with hepatocellular carcinoma

“…Our previous results, as well as the results of other reports, show that measurement of the Lens culinaris agglutinin (LCA)‐reactive species of AFP is useful for such discrimination and that the molecular basis of this variation is the fucosylation at the innermost N‐ acetylglucosamine residue of a biantennary sugar chain 8 –14 . We also reported that LCA‐reactive species of alpha‐1‐antitrypsin (AAT) and transferrin (TF) might provide useful information for the diagnosis of patients with HCC 15 –17 . This suggests that the degree of fucosylation of serum glycoproteins is a useful measurement for the diagnosis of HCC.…”

Alteration of protein glycosylation in liver diseases

“…Similar to AFP, the percentage of reactive species with the lectin Lens culinaris agglutinin was shown to be significantly higher in HCC than in benign liver diseases and normal controls [63]. Further structural analysis on the AAT-attached glycans was performed and it was shown that the fucosylated biantennary glycans were increased two-fold opposite non-fucosylated glycans [64].…”

Alteration of N‐glycan profiles in patients with chronic hepatitis and hepatocellular carcinoma

“…The serum Lens culinaris agglutinin‐reactive fraction of AFP (AFP‐L3), a well‐known component of α‐fetoprotein (AFP) with a core fucose residue, is widely used for HCC diagnosis and follow‐up surveillance as a tumor serologic marker. Haptoglobin, α1‐antitrypsin and transferrin possess altered glycosylation forms in patients with HCC.…”