Sensitization to epithelial antigens in chronic mucosal inflammatory disease. III: Serum factor modulates circulating and mucosal mononuclear-cell reactivity to epithelial cell-associated components of colon (ECAC-C)

A prior report indicated that sera together with peripheral blood mononuclear cells from patients with Crohn's disease were reactive with epithelial cell-associated components derived from small bowel (ECAC-SB). In the present study, we sought to determine whether similar components (designated...

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Bibliographic Details
Published in:Journal of clinical immunology 1987-03, Vol.7 (2), p.159-173
Main Authors: DUNKEL, G, PAUL, J. W, ROCHE, J. K
Format: Article
Language:English
Subjects:
Animals
Autoantibodies - isolation & purification
Autoantigens - immunology
Biological and medical sciences
Colitis, Ulcerative - immunology
Colon - immunology
Crohn Disease - immunology
Cytotoxicity, Immunologic
Epithelium - immunology
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Intestinal Mucosa - immunology
Leukocytes - immunology
Medical sciences
Mice
Other diseases. Semiology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
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Summary:A prior report indicated that sera together with peripheral blood mononuclear cells from patients with Crohn's disease were reactive with epithelial cell-associated components derived from small bowel (ECAC-SB). In the present study, we sought to determine whether similar components (designated ECAC-C) from everted, inflated loops of murine colon could be purified to homogeneity in aqueous soluble form and physiochemically characterized; if sera and/or peripheral mononuclear cells from patients with a chronic idiopathic inflammatory disorder of intestinal mucosa were specifically reactive with ECAC-C; whether immunoglobulin was the factor conferring specificity to the anti-ECAC-C response; and if this immunoglobulin was actively synthesized by human lamina propria B lymphocytes isolated from disease-involved intestinal mucosa. Preparative polyacrylamide gel electrophoresis followed by elution of specific bands resulted in the isolation of three major proteins in homogeneous form. Each was a distinctive macromolecule by molecular weight (39,000, 63,000, 148,000), carbohydrate/protein content, and serologically detectable determinants as assessed by quantitative hemagglutination inhibition. By a 51Cr release microcytotoxicity assay, ECAC-C-labeled indicator cells were specifically lysed by sera and peripheral blood mononuclear cells from patients with ulcerative colitis (8.0 +/- 6.8%) and Crohn's disease (13.2 +/- 4.7%), compared with age-/sex-matched controls (0.6 +/- 0.9 and 0.2 +/- 0.4%, respectively). That the factor conferring ECAC-C specificity was immunoglobulin was demonstrated by the retention of ECAC-C-specific reactivity of patient sera in the presence of normal peripheral blood mononuclear cells, the ability of patient sera (without cells) to effect complement-mediated lysis against erythrocytes labeled with ECAC-C (8.0 +/- 6.7%) but not with control kidney antigen (0.7 +/- 0.7%), and the fact that purified immunoglobulin from patient sera could substitute for the latter in an ECAC-C-specific antibody-dependent cellular cytotoxicity assay. Unique aspects of this ECAC-C reactivity included its absence from sera in other disorders with a known or presumed autoimmune basis (systemic lupus erythematosus, chronic active hepatitis) and the lack of simultaneous reactivity directed toward control antigens, isolated from kidney in a manner analogous to that used for ECAC-C. The importance of ECAC-C-specific immune responses at the mucosal level was also e
ISSN:0271-9142
1573-2592
DOI:10.1007/BF00916010