Sera from the patients with chronic liver diseases and hepatocellular carcinoma (HCC) were tested for reactivity with neutral glycosphingolipids extracted from rabbit liver plasma membrane by enzyme-linked immunosorbent assay and thin-layer chromatography immunostaining. IgG class antibody to neutral glycosphingolipids was detected in 29.6% (8 of 27), 6.3% (1 of 16), 0% (0 of 8), 0% (0 of 25), and 6.9% (2 of 29) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Using the serum positive for the antibody to neutral glycosphingolipids, the target antigen glycolipid was isolated. Negative ion fast atom bombardment mass spectrometry, exoglycosidases treatment, and permethylation analysis revealed that the main target antigen was IV3αGal-nLc4Cer. In enzyme-linked immunosorbent assay, IgG class antibody to IV3αGal-nLc4Cer was detected in 33.3% (9 of 27), 18.8% (3 of 16), 25% (2 of 8), 4% (1 of 25), and 6% (3 of 50) in the sera of patients with HCC, liver cirrhosis, autoimmune chronic active hepatitis, chronic hepatitis, and normal individuals, respectively. Of 9 HCC patients positive for the antibody, 6 had received transcatheter arterial embolization (TAE) therapy. Six of 10 patients who received TAE therapy had the antibody, whereas only 3 of 17 patients without TAE therapy had the antibody. This antibody may be a heterophile antibody, which recognizes Galα1-3Gal structure at the nonreducing terminal of the antigen. Since the occurrence of this antibody was closely related with TAE therapy, the necrosis of HCC induced by TAE therapy may stimulate the production of the antibody.

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This work was supported by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan and a grant from the Ministry of Health and Welfare of Japan.

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