ANTIBODIES TO HUMAN RECOMBINANT LIPOCORTIN-I IN INFLAMMATORY BOWEL-DISEASE

1. Corticosteroid drugs are widely employed for the treatment of activ e inflammatory bowel disease. Not all patients receiving corticosteroi d treatment, however, respond satisfactorily, their disease either rem aining active in spite of continued treatment, or relapsing upon corti costeroid withdrawal. Raised levels of autoantibodies to lipocortin-1, 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 var iable clinical response to corticosteroids in inflammatory bowel disea se, 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 le vels were elevated in patients with ulcerative colitis and Crohn's dis ease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels w ere directly related to disease activity scored clinically. 4. IgM lip ocortin-I antibody levels were higher in patients receiving sulphasala zine or no treatment and in patients receiving corticosteroids who res ponded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of conti nued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders). 5. The high levels of IgM lipocortin-I anti bodies in patients with inflammatory bowel disease not taking corticos teroids provides further evidence of disturbed immunity in inflammator y bowel disease. The low levels of IgM lipocortin-I antibody in patien ts undergoing long-term corticosteroid therapy (steroid non-responders ) contrasts with previous findings in patients with rheumatoid arthrit is and might reflect corticosteroid-induced antibody suppression and/o r depressed production of endogenous lipocortin-I antigen.