MOLECULAR EVIDENCE FOR 2 FORMS OF CROHN-DISEASE

Recent epidemiological evidence suggests that there are two forms of C rohn disease (CD): perforating and nonperforating. We hypothesized tha t,just as with tuberculoid and lepromatous leprosy, differences in the two forms of CD would be both identified and determined by difference s in the host immune response. Resected intestinal tissue from control patients as well as perforating and nonperforating CD patients was ev aluated for mRNA levels. We employed P-32 PCR amplification with publi shed or custom-designed primers of a housekeeping gene (beta-actin); a human T-cell marker (CD3-delta); and the cytokines tumor necrosis fac tor alpha, transforming growth factor beta, granulocyte/macrophage col ony-stimulating factor, interleukin (IL) 1 beta, IL-1ra, and IL-6. Dif ferences were identified with IL-1 beta (control = 162 +/- 57 vs. perf orating = 464 +/- 154 vs. nonperforating = 12,582 +/- 4733; P less tha n or equal to 0.02) and IL-1ra (control = 1337 +/- 622 vs. perforating = 2194 +/- 775 vs. nonperforating = 9715 +/- 2988; P less than or equ al to 0.02). These data corroborate the epidemiological observation th at there are two forms of CD. Nonperforating CD, the more benign form, is associated with increased IL-1 beta and IL-1ra mRNA expression. We conclude that it is the host immune response that determines which fo rm of CD becomes manifest in any given individual and discuss the inve stigative, diagnostic, and therapeutic implications of these observati ons.