Rab11 Is a Useful Tool for the Diagnosis of Microvillous Inclusion Disease

Abstract

Microvillous inclusion disease (MVID) is a congenital condition presenting with intractable diarrhea. Biopsies demonstrate abnormal apical PAS and CD10 staining in surface enterocytes correlating with the presence of characteristic cytoplasmic inclusions. MVID has been linked to mutations in myosin Vb, important in apical membrane recycling. Rab11 associates with myosin Vb in vesicle membranes and is also integral in recycling plasma membrane components. The authors performed Rab11 immunostaining on biopsies from 7 MVID cases, 10 normal small intestines, and 10 with chronic enteritis. In MVID cases, Rab11 showed diffuse apical cytoplasmic staining of surface enterocytes in a pattern similar to PAS and CD10, which was absent in all the 20 control cases. Ultrastructural examination confirmed localization to the external surface of MVID cytoplasmic inclusions. Rab11 staining may be a useful adjunct in MVID diagnosis and the results support that myosin Vb dysfunction is important in the pathogenesis of MVID.

Small GTPases of the Ras superfamily regulate intestinal epithelial homeostasis and barrier function via common and unique mechanisms

“…In another study, Rab11 has been suggested as a diagnostic marker for microvillous inclusion diseases (MVID), an intestinal disorder characterized by epithelial barrier dysfunction and diarrhea 138 . While Rab11 is located to apical membrane regions in healthy patients and those with enteritis, it translocates to the cytosol in biopsies of MVID patients.…”

Myosin 5b loss of function leads to defects in polarized signaling: implication for microvillus inclusion disease pathogenesis and treatment

“…Several apical membrane proteins are mislocalized in MVID villus enterocytes, including CD10, cystic fibrosis transmembrane conductance regulator (CFTR), sodium-hydrogen exchanger-3 (NHE3), sucrase isomaltase, alkaline phosphatase, villin, and carcinoembryonic antigen. There is also a decrease and relocalization of the Ras-related protein small GTPases Rab8 and Rab11 that reflect disruption of the apical endosomal compartment (1,15,37,47,49). Typically, these proteins relocalize to the MI, or to a subapical compartment, and are depleted in the apical pole of the cells.…”

“…Furthermore, Rab11, an ARE marker, is delocalized in MVID enterocytes (49,50). Therefore, because ARE is disrupted in MVID-affected cells (12), it was natural to speculate that PDK1, associated with the ARE, may be delocalized as well.…”

Review of Current Applications of Immunohistochemistry in Pediatric Nonneoplastic Gastrointestinal, Hepatobiliary, and Pancreatic Lesions

“…Although the periodic acid-Schiff (PAS) stain will suggest an absent positive staining at the apex of epithelial cells, along with the presence of cystic structures of variable size in the apical cytoplasm, the CD10 (Figure 8), carcinoembryonic antigen, and alkaline phosphatase IHC stains are all more sensitive 12. Antibodies against a protein on the inner lining of endosomes, Rab11a, a guanosine triphosphatase protein, also give similar positive results 13. Electron microscopy is usually confirmatory, but not necessary, if the above IHC stains are diagnostic.…”