lewis-x-antigen and Liver-Diseases

To further investigate the factors involved in the modulation of the schistosomal granuloma, mice were primed with immunogenic carbohydrates which were common to soluble egg antigen (SEA) and adult worm antigen. Mice sensitized with LewisX trisaccharide or lacto-N-fucopentaose-III (LNFP-III) displayed an increased cellular response towards SEA-coupled beads implanted in the liver by mesenteric injection, resulting in the formation of larger periparticular granulomas. When animals were sensitized with bovine serum albumin or a structurally related carbohydrate, an accelerated response was not seen. Since LNFP-III is built up of LewisX molecules, and LewisX carbohydrates are common to SEA and worm antigens such as the gut-secreted antigens CCA and CAA (two antigens that could prime egg-antigen-induced granuloma formation), this may explain why adult, live Schistosoma mansoni worms positively modulate egg-antigen-induced hepatic granuloma formation in the murine host. These observations provide new insights into the role of carbohydrates in parasite-host immunity and may yield important implications for choosing worm-derived antigens for the development of anti-schistosome vaccines.

Topics: Animals; Antigens, Helminth; Carbohydrate Sequence; Cattle; Glycoproteins; Granuloma; Helminth Proteins; Immunization; Lewis X Antigen; Liver Diseases; Mice; Molecular Sequence Data; Oligosaccharides; Schistosomiasis mansoni; Serum Albumin, Bovine; Vaccines

The serum levels of the carbohydrate antigen sialyl Lewis X (SLEX) increase in liver diseases (Sunayama T, Okada Y, Tsuji T., J Hepatol 1994; 19: 451-458). However, it is not known whether the increased serum SLEX levels are associated with the increased levels of its carrier molecules and/or the increased density of SLEX per carrier molecule. By using of rabbit antibody against an SLEX-positive fraction from HepG2 culture supernatant, we developed an enzyme-linked immunosorbent assay to determine the serum levels of the carrier molecules of SLEX (CMSLEX). The CMSLEX-levels in patients with hepatocellular carcinoma were significantly higher than those of normal controls (P < 0.001) and benign chronic liver diseases, i.e., chronic active hepatitis, mild and severe form, and liver cirrhosis (P < 0.05). Patients with chronic persistent hepatitis and chronic active hepatitis, mild form, had higher CMSLEX-levels than normal controls (P < 0.05). The serum CMSLEX-levels did not differ significantly among benign liver diseases. We concluded that serum CMSLEX-levels increase nonspecifically in liver diseases. This is a possible molecular mechanism for the increased serum SLEX levels in liver diseases.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Lewis X Antigen; Liver Diseases; Male; Middle Aged; Molecular Weight

A carbohydrate antigen, sialyl Lewis X (SLEX), is an inflammation-associated liver cell antigen, which is increasingly expressed as histological diagnosis progresses. A solid phase radioimmunoassay was developed to determine the plasma levels of this substance which were found to be elevated in about 70% of patients with liver disease, with no significant differences among disease groups. Although the plasma levels of SLEX were not directly correlated with the degree of hepatic SLEX expression, the abnormal values were only found in cases with hepatic SLEX expression. Cirrhotic patients with and without hepatocellular carcinoma had comparable values. Plasma levels of SLEX decreased significantly in chronic hepatitis patients successfully treated with IFN, but not in those without a favourable clinical response. Plasma SLEX was carried by some macromolecules with chromatographic and buoyant properties of mucin-type glycoproteins, and others of non-mucin type. These observations suggested that (i) the plasma levels of SLEX increase significantly but non-specifically in liver diseases, (ii) liver cells in the inflammatory lesion are probably the origin of the SLEX-active glycoproteins in the peripheral circulation, (iii) both the increased hepatic synthesis and impaired secretion of the SLEX-positive glycoproteins might be related to the tissue expression and plasma levels of SLEX, and (iv) plasma SLEX might be a useful marker to evaluate the activity of inflammatory liver disease in individual patients and to monitor their treatment.

Topics: Adult; Chronic Disease; Female; Glycoproteins; Hepatitis; Humans; Interferons; Lewis X Antigen; Liver Diseases; Liver Function Tests; Male; Middle Aged

Phenotypic expression of sialylated Lewis(x) antigen by means of the monoclonal antiserum SNH3 was studied in 87 livers, which included normal and steatotic livers and livers with chronic persistent and chronic active hepatitis, alcoholic hepatitis, allograft rejection, focal nodular hyperplasia, hepatocellular carcinoma, cholangiocarcinoma, metastatic carcinoma, cirrhosis of various causes (autoimmune, alcoholic, viral, drug induced, Wilson's disease, and primary biliary cirrhosis). The biotin-streptavidin-peroxidase method was used on formaldehyde-fixed, paraffin-embedded sections. Sialylated Lewis(x) antigen was not demonstrated in normal livers. Hepatocellular expression in a diffuse or perinodular honeycomb pattern was seen in cirrhosis, irrespective of cause. Sialylated Lewis(x) antigen was also observed in hepatocytes around metastatic carcinoma in the absence of inflammation, cirrhosis, or regeneration. Some bile ductules, most likely ductular hepatocytes, but not bile ducts, expressed sialylated Lewis(x) antigen. Sialylated Lewis(x) antigen was seen diffusely in fibrolamellar hepatocellular carcinoma, focally in other hepatocellular carcinomas, and either focally or diffusely in cholangiocarcinomas.

Topics: Chronic Disease; Fatty Liver; Humans; Hyperplasia; Lewis X Antigen; Liver; Liver Cirrhosis; Liver Diseases; Liver Neoplasms