Antibodies to human recombinant lipocortin-I in inflammatory bowel disease

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis. 2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome. 3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically. 4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease.(ABSTRACT TRUNCATED AT 250 WORDS)