Autoimmunity has been implicated in the pathogenesis of
ulcerative colitis (UC). Several studies have shown amplified
immunoglobulin G1 (
IgG1) antibody response in UC; however the immunoreactive
antigen(s) is unknown. To study this
antigen(s), mucosal colonic extract was prepared by sonication, ultracentrifugation followed by ion exchange chromatography in fast
protein liquid chromatography. The fraction (enriched colonic
peptide), that was most reactive to a novel
monoclonal antibody, 7E12H12 (
IgM isotype), was isolated and used to examine the immunoreactivity against the patients' serum samples. Two hundred and thirteen coded samples from 111 patients with UC (symptomatic and untreated (63), symptomatic and treated (26), remission (22)); 47 with
Crohn's disease (CD) (40 were symptomatic and untreated, and 30 had
colonic disease); 29 with acute diarrhoea caused by specific pathogen(
s); 10 with
systemic lupus erythematosus, and 16 normal subjects were examined against the enriched colonic
peptide by
IgG subtype specific
enzyme linked
immunosorbent assays (ELISAs). Total
IgG antibody reactivity was significantly (p < 0.01) higher only in symptomatic and untreated UC patients compared with each of the non-UC group, but the sensitivity was only 50%.
IgG2 and
IgG3 reactivities were not different among various groups. The
IgG1 antibody reactivity against the enriched colonic
peptide, however, differentiated UC patients from CD and each of the other non-UC groups. Seventy nine per cent of the patients with UC, treated or untreated, symptomatic or in remission, had significantly (p < 0.0001) higher
IgG1 antibody against the enriched colonic
peptide when compared with each of the other non-UC groups. Only 12% of CD serum samples and none of the other control serum samples reacted. Using purified serum
IgG1 and 7E12H12-IgM, by 7E12H12 reactive
peptide indeed reacts with UC-IgG1 antibody but not with control
IgG1.