Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge

Abstract

Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.

TG6 Auto-Antibodies in Dermatitis Herpetiformis

“…DH patients were recently shown to have TG3-antibody secreting plasma cells at the level of the gut. Importantly, a gluten challenge of such patients revealed that gluten exposure drove rapid expansion of the TG3-specific plasma cell population in the lamina propria, and their frequency correlated with the serum titer of the corresponding autoantibodies [ 17 ]. Furthermore, there was no evidence that this cell population recognizes TG isozymes other than TG3 [ 17 ].…”

“…Importantly, a gluten challenge of such patients revealed that gluten exposure drove rapid expansion of the TG3-specific plasma cell population in the lamina propria, and their frequency correlated with the serum titer of the corresponding autoantibodies [ 17 ]. Furthermore, there was no evidence that this cell population recognizes TG isozymes other than TG3 [ 17 ]. This is in keeping with the results from the analysis of patient-derived immunoglobulins, indicating that cross-reacting antibodies are rare [ 7 , 8 ].…”

Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis

“…Recently, the first studies on the occurrence of TG3 autoantibody producing cells in DH were published. Ex vivo cultures of duodenal biopsies as well as intestinal plasma cell stainings performed on DH patient tissue strongly suggest that TG3-antibody producing cells are present at least in the small intestine ( 14 , 34 ). These cells seem to be highly DH-specific: despite the occasional occurrence of circulating TG3 antibodies, TG3 antibody producing plasma cells have only rarely been detected in CeD patients ( 14 , 34 ).…”

“…Ex vivo cultures of duodenal biopsies as well as intestinal plasma cell stainings performed on DH patient tissue strongly suggest that TG3-antibody producing cells are present at least in the small intestine ( 14 , 34 ). These cells seem to be highly DH-specific: despite the occasional occurrence of circulating TG3 antibodies, TG3 antibody producing plasma cells have only rarely been detected in CeD patients ( 14 , 34 ). Furthermore, the TG3-specific plasma cells appear to be gluten-responsive as their frequency is increased during gluten challenge ( 14 ).…”

“…In CeD, TG2-antibody producing plasma cells are found in the small intestinal lamina propria ( 31 , 32 ), although circulating antibodies may originate outside the intestine despite strong clonal relatedness between circulating and gut-derived autoantibodies ( 33 ). Intestinal plasma cells producing autoantibodies against TG2 have also been discovered in DH patients ( 14 ). Recently, the first studies on the occurrence of TG3 autoantibody producing cells in DH were published.…”