Autoimmunity to heat shock proteins and vitamin D status in patients with celiac disease without associated dermatitis herpetiformis
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Tissue transglutaminase
Dermatitis herpetiformis
HSP60
Tissue transglutaminase
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Dermatitis herpetiformis
Tissue transglutaminase
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Gluten sensitivity typically presents as celiac disease, a common chronic small intestinal disorder. However, in certain individuals it is associated with dermatitis herpetiformis, a blistering skin disease characterized by granular IgA deposits in the papillary dermis. While tissue transglutaminase has been implicated as the major autoantigen of gluten sensitive disease, there has been no explanation as to why this condition appears in two distinct forms. Here we show that while sera from patients with either form of gluten sensitive disease react both with tissue transglutaminase and the related enzyme epidermal (type 3) transglutaminase, antibodies in patients having dermatitis herpetiformis show a markedly higher avidity for epidermal transglutaminase. Further, these patients have an antibody population specific for this enzyme. We also show that the IgA precipitates in the papillary dermis of patients with dermatitis herpetiformis, the defining signs of the disease, contain epidermal transglutaminase, but not tissue transglutaminase or keratinocyte transglutaminase. These findings demonstrate that epidermal transglutaminase, rather than tissue transglutaminase, is the dominant autoantigen in dermatitis herpetiformis and explain why skin symptoms appear in a proportion of patients having gluten sensitive disease.
Tissue transglutaminase
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Papillary dermis
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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). 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.
Tissue transglutaminase
Lamina propria
Immunoglobulin A
Villous atrophy
Intestinal mucosa
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Dermatitis herpetiformis is an intensely itchy, chronic, papulovesicular eruption that is usually symmetrically distributed on extensor surfaces. Histologically, it is characterized by dermal papillary collections of neutrophils and subepidermal vesicle formation. The skin has IgA deposits in areas corresponding to the earliest histopathologic change; that is, at the epidermal-dermal junction. Most patients have an associated asymptomatic gluten-sensitive enteropathy that mimics ordinary glutensensitive enteropathy (celiac disease) both morphologically and in its response to gluten protein. There is a marked increase in the prevalence of the major histocompatibility antigens, HLA-B8 and HLA-Dw3, and in certain B cell antigens in these patients. Although the sulfones or sulfapyridine have been the mainstay of treatment, it is now clear that the skin disease responds to strict adherence to a gluten-free diet. These findings are reviewed and from them are drawn certain conclusions as to possible pathophysiologic mechanisms involved in dermatitis herpetiformis.
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Dermal papillae
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Tissue transglutaminase (tTG) is an autoantigen in coeliac disease and the related disorder, dermatitis herpetiformis. The detection of autoantibodies directed against tTG is a highly specific marker of coeliac disease; however, it is unclear if there is a role for these autoantibodies in the disease process. The aim of this study was to investigate whether the catalytic triad of tTG is targeted by coeliac disease autoantibodies.A full-length wild-type recombinant tTG and a novel site-directed mutagenic variant lacking the catalytic triad were produced in Escherichia coli. Serum samples from 61 biopsy-proven coeliac disease and 10 dermatitis herpetiformis patients were tested for their recognition of both antigens in enzyme-linked immunosorbent assay.Although IgA autoantibodies from sera of patients with coeliac disease and dermatitis herpetiformis bound wild-type tTG well, a dramatic decrease in binding to the mutant tTG was observed with a mean reduction of 79% in coeliac disease and 58% in dermatitis herpetiformis samples. IgG anti-tTG antibodies did not show a similar pattern of reduction, with no overall difference in recognition of the wild-type or mutant tTGs.These results suggest that the IgA anti-tTG response in coeliac disease and dermatitis herpetiformis is focused on the region of tTG responsible for its transamidation and deamidation reactions, whereas the IgG response may target other regions of the enzyme.
Dermatitis herpetiformis
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Tissue transglutaminase
Dermatitis herpetiformis
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A study was undertaken to determine whether the skin eruption of linear IgA disease (LAD) was gluten dependent. Six patients with LAD were treated with a gluten free diet (GFD) for an average period of 33 months (range 19-48). Although one patient with LAD had an enteropathy which was clearly gluten sensitive, there was no convincing evidence that the rash of any of the patients responded to a GFD. Four of the six patients showed no significant alteration in their drug requirements. The remaining 2 patients showed a fall in minimum drug requirement but there was no increase after gluten challenge indicating that they were entering spontaneous remission. This contrasts to the situation in dermatitis herpetiformis, where both the rash and the enteropathy are gluten dependent. These data add further to the evidence that LAD and dermatitis herpetiformis are separate entities.
Dermatitis herpetiformis
Gluten free
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About two thirds of the patients with dermatitis herpetiformis have an enteropathy which responds to treatment with a gluten-free diet. By contrast, their rash is totally unaffected by gluten withdrawal. Likewise, the rash is unaffected by gluten withdrawal in patients with dermatitis herpetiformis who have a normal bowel. Intradermal injection of gluten does not provoke the rash. The significance of the dose of dapsone required to control the rash is discussed. The minimal effective dose of dapsone is in most patients unaffected by gluten withdrawal. The relationship of the enteropathy to the rash is an indirect one and patients whose enteropathy is controlled by a gluten-free diet will still need dapsone for their rash.
Dermatitis herpetiformis
Dapsone
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