Phenotypic Analysis of Disease-Relevant T Cells in Dermatitis Herpetiformis

Separate Gut Plasma Cell Populations Produce Auto‐Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis

“…All the DH patients studied here have prominent B‐cell responses to TG2, and the fact that DH patients have T cells reactive with deamidated gluten peptides [ 4e ] leads us to hypothesize that DH patients, as regular CeD patients, develop an immune response to gluten involving gluten–TG2 complexes. Such complexes facilitate interactions between TG2‐specific B cells and gluten‐specific CD4 + T cells, leading to the generation of TG2‐specific plasma cells as well as clonal amplification of long‐lived gluten‐specific T cells.…”

“…[ 3 ] Both diseases demonstrate the same strong association to the human leukocyte antigen (HLA)‐DQ allotypes DQ2.5, DQ2.2, and DQ8, and both types of patients have CD4 + T cells specific for deamidated gluten peptides. [ 4 ] In both diseases, the immune response to gluten drives the generation of auto‐antibodies to transglutaminase enzymes; in CeD to transglutaminase 2 (TG2) and in DH to transglutaminase 3 (TG3) as well as to TG2. [ 5 ] Transglutaminases are a family of enzymes characterized by Ca 2+ ‐dependent and sequence‐specific targeting of polypeptide glutamine residues, leading either to crosslinking via attachment of the side chain to a primary amine (such as a lysine residue; transamidation) or conversion into glutamic acid through hydrolysis (deamidation).…”