Background/aims: Increased intestinal permeability is observed in Crohn's disease and a subset of first-degree relatives. An alteration in isoform expression of the common leukocyte antigen (CD45) is also found in a significant fraction of patients. Because this alteration may be a measure of antigen exposure, the hypothesis of the study was that this alteration would be observed in both patients and relatives of patients with Crohn's disease and that this would correlate with increased intestinal permeability.
Methods: Lactulose and mannitol permeability were defined in healthy controls, patients with Crohn's disease, and their first-degree relatives. Simultaneously, peripheral blood was assayed using flow cytometry for CD45RO expression on CD19+ B cells.
Results: A subset of relatives had significantly increased permeability, as did the majority of patients with Crohn's disease. A small fraction of peripheral B cells from controls expressed the CD45 isoform (< 6%). This fraction was significantly increased for patients with Crohn's disease and their relatives. Relatives with no clinical evidence of Crohn's disease were only found to have increased CD45RO expression if they had increased permeability.
Conclusions: Individuals at risk for developing Crohn's disease include a subset with increased intestinal permeability. These people have an associated phenotypic alteration of circulating B cells that is not observed in controls or relatives with normal intestinal permeability.