DISTINCT PRODUCTION OF AUTOANTIBODIES TO NUCLEAR-COMPONENTS IN ULCERATIVE-COLITIS AND IN CROHNS-DISEASE

Despite extensive research, the pathogenesis of inflammatory bowel dis eases (IBD) is still unclear. Immunological disorders have been descri bed in patients with both Crohn's disease (CD) and ulcerative colitis (UC). In this work serum samples collected from 58 patients with CD an d 55 patients with UC were tested in ELISA against a panel of nuclear and cytoplasmic proteins and peptides in order to determine whether sp ecific autoantibodies are produced in these patients. Low levels of Ig G antibodies to histones H1, H2A, H2B, H3, and H4, to Hsp-70 and ubiqu itin stress proteins, Ro/SSA and La/SSB proteins and myosin were detec ted in some of these sera. In contrast, the following antibodies of Ig G isotype could be much more frequently demonstrated: antibodies to ub iquitinated H2A (U-H2A) peptide T4 (51.7% in CD; 18.2% in UC), antibod ies to the zinc finger peptide F2 of poly(ADP-ribose polymer)ase (PARP ) involved in DNA repair (58.6% in CD; 25.5% in UC) and actin antibodi es (43.1% in CD; 7.3% in UC). In a follow-up study of 12 patients with CD and UC (75 additional samples), we found IgG antibodies to several histone peptides occurring essentially in the serum of patients with CD. Although we found no obvious correlation between the presence or l evel of these various antibodies and C-reactive protein, or the locati on of the disease, in a number (but not all) of patients, we observed a strikingly good relationship between antibodies to histone peptides, U-H2A peptide T4, and PARP peptide F2 and the Crohn's disease activit y index. The mechanism of induction of these antibodies still remains obscure. However, since the pattern of antibodies in patients with CD seems to be different compared to that of UC, the present results may be important to follow both diseases which are sometimes difficult to distinguish on the basis of clinical data alone. (C) 1995 Academic Pre ss, Inc.