Specific Circulating Anti-Gliadin IgG-Class Antibody Does Not Mediate Intestinal Enteropathy in Gliadin-Fed Mice

Abstract

The effects of specific circulating IgG antibody on the uptake of dietary antigen and in the generation of intestinal enteropathy have been investigated in Balb/c mice bred on a gluten-free diet. A monoclonal IgG1 antibody (GD3) was prepared against gliadin. After adoptive transfer into mice, this antibody was capable of mediating a type III hypersensitivity response in vivo to footpad challenge with gliadin. The titres of circulating GD3, as estimated in vitro by ELISA, correlated well with the degree of inflammation at sites of type III responses in vivo. Following footpad challenge with gliadin, titres of circulating GD3 antibody were reduced. GD3 antibody was tested for its ability to mediate inflammatory responses in vivo in the intestinal mucosa of mice fed with gliadin. Circulating GD3 antibody was removed selectively and specifically by dietary gliadin, compared to feeding with bovine serum albumin or maintenance on a gliadin-free diet only. However, we were unable to demonstrate any pathological changes in the intestine as a result of possible local antigen-antibody complex formation or deposition. Using radio-iodinated gliadin as a trace marker, no significant retention of gliadin in the intestinal mucosa was found in mice pre-injected with GD3 antibody. These data suggest that circulating IgG antibody has little effect on dietary antigen uptake in the gut, and alone is insufficient to mediate an enteropathy.

Antibodies in celiac disease: implications beyond diagnostics

“…Neither passive transfer of IgG-class gliadin Antibodies in celiac disease S Caja et al 105 antibodies 83 nor adenovirus vector-mediated expression of celiac patient-derived TG2-specific autoantibodies in mice 82 have resulted in any kind of intestinal pathology resembling that seen in human celiac disease. Similarly, experiments to immunize mice with the celiac disease autoantigen TG2 failed to induce any morphological changes in the small bowel.…”

In vitromodels for gluten toxicity: relevance for celiac disease pathogenesis and development of novel treatment options

“…A number of attempts have been made to create an animal model for celiac disease by various approaches. These include the generation of transgenic mice expressing the celiac-type human HLA DQ2 or DQ8 11–14 and introduction of celiac-type antibodies in mice, 15–17 but none of the animals used have developed a full-blown villous atrophy together with crypt hyperplasia that are characteristic for untreated celiac disease. Gluten-dependent small-intestinal mucosal damage can be induced in mice 18 and has been described in rhesus macaques, 19 but these two models are not dependent on celiac-type HLA and their applicability as models for celiac disease has thus to be considered with caution.…”