Epithelial deposits of immunoglobulin G1 and activated complement colocalise with the M(r) 40 kD putative autoantigen in ulcerative colitis.
The intestinal expression pattern and general tissue distribution of the M(r) 40 kD putative epithelial autoantigen in ulcerative colitis were re-examined by in situ two and three colour immunofluorescence staining including the murine monoclonal antibody 7E12H12. The intestinal distribution was also compared with the epithelial codeposition of IgG1 and activated complement (C3b and terminal complement complex) seen selectively in ulcerative colitis. The M(r) 40 kD antigen was found for the first time in goblet cells of normal terminal ileum and proximal colon but not in rectal goblet cells. By contrast, colonic enterocytes expressed this antigen apically with increasing intensity in a distal direction, expanding to intense cytoplasmic expression in rectal enterocytes. The antigen was also expressed by the epithelium of the fallopian tubes, major bile ducts, gall bladder, and epidermis but not by proximal gastrointestinal tract epithelium or 13 other extra-gastrointestinal organs. Activated complement and IgG1 often colocalised with the M, 40 kD antigen apically on the surface epithelium in active ulcerative colitis but not in Crohn's disease. Our results support the idea that an autoimmune response to this antigen, leading to complement activation mediated by IgG1, is a possible pathogenetic mechanism for epithelial damage and persistent inflammation in ulcerative colitis.
Halstensen
T S
TS
Laboratory for Immunohistochemistry and Immunopathology, University of Oslo, National Hospital, Norway.
Das
K M
KM
Brandtzaeg
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000032:analysis*; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology*; D008875:Middle Aged; D008970:Molecular Weight
D001324:Autoantigens; D007074:Immunoglobulin G; D003165:Complement System Proteins