The differential expression of a novel intestinal epithelial glycoprotein in various forms of inflammatory bowel disease.
A13D8 is a monoclonal IgM antibody that identifies an as yet unknown antigen that is expressed intensely and ubiquitously in enterocytes. Immunohistochemically, it was shown that A13D8 has a granular supranuclear staining pattern in columnar epithelial cells of normal small intestine and the colon. In ulcerative colitis, this staining pattern was retained. However, during active inflammation, staining also was evident in goblet cells. To test whether this feature of goblet cell staining was unique to ulcerative colitis, tissue sections from a variety of colitides were examined. Crohn's disease, infectious colitis, and ischemic colitis had similar staining patterns to that seen with ulcerative colitis. There was significantly more inflammation in the biopsies from patients with ulcerative colitis and Crohn's disease with positive goblet cell staining than in the biopsies from those patients with negative goblet cell staining. Almost all positive goblet cell staining in ulcerative colitis and Crohn's disease occurred in biopsies that were actively inflamed, whereas there was rare staining in biopsies that were noninflamed (regardless of whether or not there was active inflammation elsewhere in the colon). Ileal goblet cells stained positively with A13D8 only in cases of active ileitis. In cases of collagenous colitis, with comparable degrees of inflammation to that seen in ulcerative colitis and Crohn's disease, there was rarely goblet cell staining and in graft-versus-host disease goblet cell staining of A13D8 was not observed. The binding of A13D8 to tissue sections was completely inhibited by N-acetyl-D-galactosamine. These results, in conjunction with immunochemical studies, suggest that the antibody recognizes an N-acetyl-D galactosamine-containing epitope on a glycoprotein(s). In conclusion, these data suggest that A13D8 recognizes a glycoprotein expressed by intestinal columnar epithelial cells and during specific inflammatory states, particularly those associated with a neutrophilic infiltrate, becomes evident in goblet cells. Further work is required to establish the exact nature of this molecule and whether it is a pro- or anti-inflammatory factor.
Bernstein
C N
CN
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Pettigrew
N M
NM
el-Gabalawy
H S
HS
Sargent
M
M
Meu
Y
Y
Wilkins
J
J
D000911:Antibodies, Monoclonal / Q000737:chemistry; D000941:Antigens / Q000737:chemistry / Q000276:immunology; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000473:pathology*; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000473:pathology*; D007424:Intracellular Fluid / Q000737:chemistry; D013194:Staining and Labeling; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000941:Antigens; D006023:Glycoproteins