Molecular evidence for two forms of Crohn disease.

Abstract

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 employed 32p PCR amplification with published or custom-designed primers of a housekeeping gene (13-actin); a human T-cell marker (CD3-6); and the cytokines tumor necrosis factor a, transforming growth factor (3, granulocyte/macrophage colony-stimulating factor, interleukin (IL) 1(3, IL-lra, and IL-6. Differences were identified with IL-1,B (control = 162 ± 57 vs. perforating = 464 ± 154 vs. nonperforating = 12,582 ± 4733; P c 0.02) and IL-lra (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-1,B and IL-lra 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.

On the etiology of Crohn disease.

“…The diagnosis, demographic data, disease duration, and histopathological features of this patient population have been presented in detail (24). All patients were having clinically indicated intestinal resections.…”

“…Although controversial (18,19) there is clinical (20,21), epidemiological (22), and molecular (23,24) evidence indicating that there are two distinct clinical manifestations of CD. These CD subclassifications have been designated as "perforating" and "nonperforating" forms (22).…”

“…Samples from this cohort had previously been used in a study that demonstrated a difference in the cytokine profiles between the two CD subpopulations (24). In this study, we employ reverse transcription (RT)-PCR amplification to probe for the presence of a M. paratuberculosis-specific DNA sequence (IS 900) (26).…”

Prediction of the Need for Surgical Intervention in Obstructive Crohn's Disease by 18F-FDG PET/CT

“…On the basis of clinical-pathologic behavior, 3 subtypes of CD have been described: stricturing, penetrating, and inflammatory (or nonstricturing/nonpenetrating) (2,3). For patients with the stricturing subtype, inflammation and accompanying cytokines lead to a pattern of muscle hypertrophy and collagen production from myofibroblasts over 8-10 y.…”

Cell Wall-Deficient Bacteria as a Cause of Infections: A Review of the Clinical Significance

“…95 In contrast, the perforating type of Crohn's disease is characterized by fistulae formation, abscesses, and has been likened to lepromatous leprosy. It is thought that the immune response of the individual determines which of the two disease types manifests clinically.…”