Molecular Evidence for Two Forms of Crohn Disease

Recent epidemiological evidence suggests that there are two forms of Crohn disease (CD): perforating and nonperforating. We hypothesized that, just as with tuberculoid and lepromatous leprosy, differences in the two forms of CD would be both identified and determined by differences in the host immun...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 91; no. 26; pp. 12721 - 12724
Main Authors E. C. A. M. Gilberts, Greenstein, A. J., Katsel, P., Harpaz, N., Greenstein, R. J.
Format Journal Article
LanguageEnglish
Published United States National Academy of the Sciences of the United States of America 20.12.1994
National Acad Sciences
National Academy of Sciences
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Summary:Recent epidemiological evidence suggests that there are two forms of Crohn disease (CD): perforating and nonperforating. We hypothesized that, just as with tuberculoid and lepromatous leprosy, differences in the two forms of CD would be both identified and determined by differences in the host immune response. Resected intestinal tissue from control patients as well as perforating and nonperforating CD patients was evaluated for mRNA levels. We employed32P PCR amplification with published or custom-designed primers of a housekeeping gene (β-actin); a human T-cell marker (CD3-δ); and the cytokines tumor necrosis factor α, transforming growth factor β, granulocyte/macrophage colony-stimulating factor, interleukin (IL) 1β, IL-1ra, and IL-6. Differences were identified with IL-1β (control = 162 ± 57 vs. perforating = 464 ± 154 vs. nonperforating = 12,582 ± 4733; P ≤ 0.02) and IL-1ra (control = 1337 ± 622 vs. perforating = 2194 ± 775 vs. nonperforating = 9715 ± 2988; P ≤ 0.02). These data corroborate the epidemiological observation that there are two forms of CD. Nonperforating CD, the more benign form, is associated with increased IL-1β and IL-1ra mRNA expression. We conclude that it is the host immune response that determines which form of CD becomes manifest in any given individual and discuss the investigative, diagnostic, and therapeutic implications of these observations.
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ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.26.12721