Coeliac disease: the paradox of diagnosing a food hypersensitivity disorder with autoantibodies.

Serum antibodies to the autoantigen transglutaminase 2 (TG2) are increasingly harnessed to diagnose coeliac disease. Diagnostic guidelines for children give recommendation for a no-biopsy-based diagnosis through detection of high amounts of IgA anti-TG2 antibodies in serum with confirmation of positivity in a separate blood sample by characteristic autoantibody-staining of tissue. While measurement of IgA anti-TG2 also is important in the diagnostic workup of adults, the adult guidelines still mandate examination of gut biopsies.

Transglutaminase 2 affinity and enzyme-substrate intermediate stability as determining factors for T-cell responses to gluten peptides in celiac disease.

The adaptive immune response of celiac disease (CeD) involves presentation of gluten peptides to CD4 T cells by transglutaminase 2 (TG2) specific B cells. This B-cell/T-cell crosstalk is facilitated by involvement of TG2:gluten peptide complexes that act principally in the form of enzyme-substrate intermediates. Here, we have addressed how gluten peptide affinity and complex stability in the presence of secondary substrates affect the uptake of TG2:gluten peptide complexes by TG2-specific B cells and the activation of gluten-specific T cells.

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

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).

TG2-gluten complexes as antigens for gluten-specific and transglutaminase-2 specific B cells in celiac disease.

A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones.