Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis

Abstract

Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.

The risk of renal comorbidities in celiac disease patients depends on the phenotype of celiac disease

“…In celiac disease, the autoantibodies target tissue transglutaminase (TG2), whereas in dermatitis herpetiformis autoantibodies are generated against both TG2 and epidermal transglutaminase (TG3). These differences in immunological processes may affect the systemic nature of the disease phenotypes [ 3 , 4 , 34 ]. Moreover, a slightly increased mortality risk has been observed in patients with celiac disease, whereas the mortality rate in dermatitis herpetiformis is decreased [ 2 , 4 ].…”

Gluten Intolerance and Its Association With Skin Disorders: A Narrative Review

“…In another study, excessive production of Th2-related cytokines, such as interleukin (IL)-4 and IL-5, was identified in the serum of patients with dermatitis herpetiformis, both in their skin and blood circulation [ 10 ]. Diagnosis of dermatitis herpetiformis hinges on the accumulation of immunoglobulin IgA in the papillary dermis.…”

Antibody Responses to Transglutaminase 3 in Dermatitis Herpetiformis: Lessons from Celiac Disease

“…Complexes originating from the circulation are also supported by findings of TG3 being present in serum [ 15 ]. The complexes of TG3 and IgA are found on the dermal–epidermal boundary, where TG3 is not endogenously expressed [ 51 ]. While TG3–IgA complexes are a characteristic feature in DH, they do not seem to be pathogenic by themselves, as they are often found in areas of the skin adjacent to the actual lesions in DH [ 52 , 53 ], as well as occasionally also in CeD patients not exhibiting any DH symptoms [ 54 , 55 , 56 ].…”