MUCOSAL ANTIBODIES IN INFLAMMATORY BOWEL-DISEASE ARE DIRECTED AGAINSTINTESTINAL BACTERIA

In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD ) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To in vestigate the specificities of these antibodies mucosal immunoglobulin s were isolated from washings taken at endoscopy from 21 control patie nts with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative col itis (UC, 20 active, seven inactive). Total mucosal IgG was much highe r (p<0.001) in active UC (median 512 mu g/ml) and active CD (256 mu g/ ml) than in irritable bowel syndrome controls (1.43 mu g/ml), but not significantly different from controls with non-IBD intestinal inflamma tion (224 mu g/ml). Mucosal IgG bound to proteins of a range of non-pa thogenic commensal faecal bacteria in active CD; this was higher than in UC (p<0.01); and both were significantly greater than controls with non-IBD intestinal inflammation (CD p<0.001, UC p<0.01) or IBS (p<0.0 01 CD and UC). This mucosal IgG binding was shown on western blots and by enzyme Linked immunosorbent assay (ELISA) to be principally direct ed against the bacterial cytoplasmic rather than the membrane proteins . Total mucosal IgA concentrations did not differ between IBD and cont rols, but the IgA titres against faecal bacteria were lower in UC than controls (p<0.01). These experiments show that there is an exaggerate d mucosal immune response particularly in active CD but also in UC dir ected against cytoplasmic proteins of bacteria within the intestinal l umen; this implies that in relapse of IBD there is a breakdown of tole rance to the normal commensal flora of the gut.