Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain.
Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.
Laboratory for Immunohistochemistry and Immunopathology, University of Oslo, Norway.
K
K
Kett
H
H
Scott
O
O
Fausa
P
P
Brandtzaeg
D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007070:Immunoglobulin A / Q000145:classification; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007133:Immunoglobulin Joining Region / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007583:Jejunum / Q000166:cytology / Q000276:immunology; D008297:Male
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007133:Immunoglobulin Joining Region