SUMMARYMaternal IgG is transferred to the suckling mouse and rat through a major histocompatibility complex (MHC ) class I-related Fc receptor (FcRn) on the brush border of the proximal small intestine. We have previously described a site on the epithelial surface of the human fetal intestine with IgG binding characteristics similar to FcRn. We report here the identification by reverse transcriptase polymerase chain reaction amplification and sequencing of the human orthologue of rat and mouse FcRn in tissue obtained from human fetal and adult intestine. FcRn protein was detected in adult human intestine by western blot. Immunohistochemical studies of sections of human intestine show that the FcRn is localized mostly to the epithelial cells, where it is in the apical region. These data suggest that the binding of IgG previously seen in the fetal intestine is due to the presence of FcRn. Potential roles for this MHC class I-like Fc receptor in the human intestine include the transfer of passive immunity, induction of oral tolerance, and immunosurveillance.

The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have previously found unusually low IgG concentrations in sera of mice homozygous for a targeted disruption of the β2‐microglobulin gene. We therefore investigated whether this might result, at least in part, from increased clearance of IgG from the systemic circulation in mice lacking β2‐microglobulin. We compared the half‐lives of radiolabelled mouse IgG1 injected intravenously into β2‐microglobulin−/− mice and wild‐type or heterozygous siblings. The clearance of 125I‐labelled IgG1 was strikingly more rapid in the mice lacking β2‐microglobulin. β2‐microglobulin−/− mice lack functional molecules of the MHC class I‐related Fc receptor, FcRn. Some mutations in mouse IgG1 that increase its clearance have recently been shown to prevent binding to FcRn in the gut. To determine whether the slower degradation of immunoglobulin in mice with β2‐microglobulin correlated with the ability of the antibody to bind FcRn, we measured the clearance of chicken IgY, which does not bind this receptor. The 125I‐labelled IgY was catabolized equally rapidly in β2‐microglobulin‐deficient and wild‐type mice. We compared the half‐lives of the four subclasses of mouse IgG in β2‐microglobulin−/−, +/−, and +/+ mice to determine whether the difference we had noted for IgG1 was peculiar to this subclass. The 125I‐labelled IgG of all subclasses, with the possible exception of IgG2b, was degraded more rapidly in the β2‐microglobulin‐deficient mice than in heterozygous or wild‐type siblings. These data suggest that FcRn can protect IgG from degradation, and is therefore important in maintaining IgG levels in the circulation.

Background Obesity is a significant public health threat to children in the United States. Aims 1) Determine the prevalence of obesity in a multi-center cohort of children with IBD; 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. Methods We used data from the ImproveCareNow Collaborative for pediatric IBD, a multi-center registry of children with IBD, collected between April 2007 and December 2009. Children ages 2-18 years were classified into BMI percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI>85%) and obese (BMI>95%) status. Results The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohn's disease (CD) and 30.1% for ulcerative colitis (UC) and indeterminate colitis (IC)). African American race (OR 1.64, 95% CI 1.10-2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19-2.34) were positively associated with overweight/obese status. Prior IBD related surgery (OR 1.73, 95% CI 1.07-2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. Conclusions Approximately 1/5 of children with CD and 1/3 with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population.