Injection of prototypic celiac anti-transglutaminase 2 antibodies in mice does not cause enteropathy

PLoS One. 2022 Apr 6;17(4):e0266543. doi: 10.1371/journal.pone.0266543. eCollection 2022.

Abstract

Background: Celiac disease is an autoimmune enteropathy driven by dietary intake of gluten proteins. Typical histopathologic features are villous flattening, crypt hyperplasia and infiltration of inflammatory cells in the intestinal epithelium and lamina propria. The disease is hallmarked by the gluten-dependent production of autoantibodies targeting the enzyme transglutaminase 2 (TG2). While these antibodies are specific and sensitive diagnostic markers of the disease, a role in the development of the enteropathy has never been established.

Methods: We addressed this question by injecting murine antibodies harboring the variable domains of a prototypic celiac anti-TG2 immunoglobulin into TG2-sufficient and TG2-deficient mice evaluating for celiac enteropathy.

Results: We found no histopathologic abnormalities nor clinical signs of disease related to the injection of anti-TG2 IgG or IgA.

Conclusions: Our findings do not support a direct role for secreted anti-TG2 antibodies in the development of the celiac enteropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies
  • Celiac Disease* / pathology
  • GTP-Binding Proteins / metabolism
  • Glutens / metabolism
  • Immunoglobulin A
  • Intestinal Mucosa / metabolism
  • Mice
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases* / metabolism

Substances

  • Autoantibodies
  • Immunoglobulin A
  • Glutens
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins

Grants and funding

This work was supported by grants from the Research Council of Norway (project 275053 to L.M.S.), the European Commission (project ERC-2010-Ad-268541 to L.M.S.), and the University of Oslo. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.