Circulating autoantibodies against purified colonic mucin in ulcerative colitis

To clarify the role of colonic mucin in the autoimmune process of ulcerativ e colitis, circulating antibodies against human colonic mucin were investig ated. Purified colonic mucin, obtained from human colonic mucosa by gel fil tration, using a Bio-Gel A-1.5-m column and CsCl equilibrium density gradie nt, was divided into soluble mucin (S-mucin) secreted extracellularly and m embranous mucin (M-mucin) binding to cell membrane. Sodium dodecylsulfate p olyacrylamide gel electrophoresis and Western blotting analysis showed that antibodies in the serum samples of some patients with ulcerative colitis r ecognized purified S- and M-mucin of >180-kD. By enzyme-linked immunosorben t assay (ELISA), anti-mucin antibodies were detected in 11 of 60 patients w ith ulcerative colitis (18%). In contrast, the antibodies were not detected in 22 patients with Crohn's disease. The titers of antimucin antibodies ag ainst: S-mucin and M-mucin were not different in each patient. By ELISA usi ng mucin in which the sugar chains were destroyed by neuraminidase or NaIO4 treatment, it was demonstrated that anti-mucin antibodies recognized the e pitopes of either the sugar chain or the core protein exposed through destr uction of the sugar chains. We then investigated the relationship between a nti-mucin antibodies and the patients' clinical features. Anti-mucin antibo dies were detected in 6 of 15 patients with chronic continuous type ulcerat ive colitis (40%) and in 5 of 26 patients with relapsing-remitting type (19 %), but there was no antimucin antibody-positive serum in patients who had had only one attack without any relapse. These results suggest that anti-mu cin antibodies could be a disease marker for ulcerative colitis and that im munological abnormalities in colonic mucin contribute to the persistence of colonic mucosal inflammation.