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Mucosal t-cell immunoregulation varies in early and late crohn's disease
  1. Subra Kugathasan MD (skuga{at}mcw.edu)
  1. Medical College of Wisconsin, United States
    1. Lawrence Sauberman
    1. Harvard Medical School, United States
      1. Larry Smith
      1. Apollon Inc, wyeth-lederle Vaccines & Pediatrics, United States
        1. Douglas Kou
        1. Case Western Reserve University, United States
          1. Jugoh Itoh
          1. Case Western Reserve University, United States
            1. David Binion
            1. Medical College of Wisconsin, United States
              1. Alan levine
              1. Case Western Reserve University, United States
                1. Richard Blumberg
                1. Harvard Medical School, United States
                  1. Claudio Fiocchi MD (fiocchc{at}ccf.org)
                  1. Cleveland Clinic Foundation, United States

                    Abstract

                    Background & Aims: Crohn's disease (CD) is a life-long form of inflammatory bowel disease (IBD) mediated by mucosal immune abnormalities. Understanding of pathogenesis is limited because based on data from adults with chronic CD. We investigated mucosal T-cell immunoregulatory events in children with early CD.

                    Methods: Mucosal biopsies and T-cell clones were derived from children experiencing the first attack of CD, children with longstanding CD, infectious colitis, and children without gut inflammation.

                    Results: As in acute infectious colitis, IL-12 induced T-cells from early CD to acquire a strongly polarized Th1 response characterized by high IFN-production and IL-12R2 chain expression. Th1 polarization was not induced in clones from late CD. Mucosal levels of IL-12p40 and IL-12R2 mRNA were significantly higher in children with early than late CD. These results demonstrate that susceptibility to IL-12-mediated modulation is strongly dependent on the stage of CD.

                    Conclusions: At the onset of CD mucosal T-cells appear to mount a typical Th1 response that resembles an acute infectious process, and is lost with progression to the late CD. This suggests that mucosal T-cell immunoregulation varies with the course of human IBD. Patients with the initial manifestations of IBD may represent an ideal population in where immunomodulation may have optimal therapeutic efficacy.

                    • Crohn's disease
                    • IBD
                    • children
                    • pathogenesis
                    • ulcerative colitis

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