Aberrant expression of MUC1 mucin in pediatric inflammatory bowel disease.
Mucin 1 (MUC1) glycoprotein is normally expressed at low levels on the luminal side of healthy colonic epithelial cells. In colon cancer and other epithelial tumors, MUC1 is overexpressed and hypoglycosylated. Antibodies specific for this "tumor form" of MUC1 are found in cancer patients. We hypothesized that MUC1 expression might be altered in chronic inflammation, such as in inflammatory bowel disease (IBD). Furthermore, we hypothesized that these alterations might induce antibody responses. The aims of this study were to characterize MUC1 expression in IBD and to examine whether pediatric patients with IBD have an MUC1-specific antibody. Colon biopsies were examined for MUC1 expression by immunochemistry using anti-MUC1 antibodies that detect normal or abnormal forms of MUC1. Sera were analyzed by Enzyme Linked Immunosorbent Assay (ELISA) for evidence of anti-MUC1 antibody. We found marked overexpression of MUC1 in IBD, most of which was hypoglycosylated. On colon specimens from healthy age-matched controls, we found low levels of luminal MUC1 and no alteration in its glycosylation. We detected antibody to MUC1 in sera of IBD patients as well as controls, and in a limited number of IBD samples examined longitudinally, we could correlate the rise and fall of antibody levels with clinical disease severity. MUC1 is overexpressed and hypoglycosylated in pediatric IBD and may play an important role in the pathogenesis of IBD, and thus warrants further study as a potential therapeutic target. Similarly, antibodies to MUC1 may influence IBD and should be explored as potential diagnostic or prognostic markers.
Furr
Anna E
AE
Department of Pediatric Gastroenterology, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
Ranganathan
Sarangarajan
S
Finn
Olivera J
OJ
D015415:Biomarkers; D001706:Biopsy; D002648:Child; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D018396:Mucin-1 / Q000378:metabolism*
D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1