Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet
Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten-sensitive enteropathy (celiac disease). Patients with DH demonstrate circulating IgA antibodies against epidermal transglutaminase (eTG) and tissue transglutaminase (tTG). It has been suggested that eTG is the autoantigen of DH.
The purpose of this study was to characterize the autoimmune response to eTG and tTG in patients with DH on a normal or gluten-free diet (GFD).
Sera from 52 patients with DH were studied for the presence of IgA antibodies to eTG and tTG by enzyme-linked immunosorbant assay. In 38 patients, serum was obtained before initiation of a GFD, whereas 14 patients had been on a GFD for at least 2 years.
Autoantibodies against eTG were detected in 36 of 38 patients (95%) and those against tTG in 30 of 38 patients (79%) with DH on a normal diet. Of 14 patients on a long-term GFD, 7 patients were free of DH lesions and did not require dapsone treatment. None of these patients showed circulating antibodies against eTG or tTG. The remaining 7 patients on a GFD were not able to stop taking dapsone. All these patients demonstrated anti-eTG antibodies, whereas only 3 of them showed additional reactivity against tTG.
Autoantibody levels against eTG and tTG before and after introduction of a GFD were not examined in the same patients.
Our data suggest that antibodies to eTG are the most sensitive serologic marker in treated and untreated patients with DH and confirm the central role of eTG in the pathogenesis of this disease.
Available from: Stefan Tukaj
- "In addition to the observed significant positive correlation between autoantibodies against Hsp60, Hsp70, and Hsp90 and the cutaneous disease activity of DH patients, a significant positive relationship was found between the humoral autoimmune response towards these Hsp and levels of circulating autoantibodies against eTG and tTG, which also decreased significantly during follow-up of our patients. Autoantibodies against eTG are believed to play a central role in the pathogenesis and maintenance of the cutaneous disease in patients with DH (Sárdy et al. 2002; Rose et al., 2009), while autoantibodies to tTG are known to reflect the extent of histopathologic changes of the small bowel and to decrease under a gluten-free diet (Caproni et al. 2001; Tursi et al. 2003). "
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ABSTRACT: Heat shock proteins (Hsp) are highly conserved immunomodulatory molecules upregulated when cells are exposed to stressful stimuli, such as inflammation. Their involvement in various autoimmune diseases, including autoimmune bullous diseases and celiac disease, has been increasingly recognized. To further study the role of Hsp in autoimmune bullous diseases, we have investigated for the first time the humoral autoimmune response to Hsp40, Hsp60, Hsp70, and Hsp90 in patients with dermatitis herpetiformis (DH; n = 26), bullous pemphigoid (BP; n = 23), and pemphigus vulgaris (PV; n = 16), the first representing a cutaneous manifestation of celiac disease. While in patients with active BP and PV, serum levels of autoantibodies against these Hsp did not differ from the corresponding age- and gender-matched healthy controls (n = 9-14); circulating autoantibodies against Hsp60, Hsp70, and Hsp90 were found to be increased at the active disease stage of DH. Further analysis of this latter patient subgroup showed that these anti-Hsp autoantibodies decreased in parallel with serum autoantibodies against epidermal and tissue transglutaminase during remission of skin lesions following a gluten-free diet, revealing significantly positive correlations. Although further studies on larger groups of patients will be needed to confirm the present data, our results support the notion that autoantibodies against Hsp60, Hsp70, and Hsp90 deserve attention in the study of the mechanisms that promote the development and maintenance of DH and possibly also the underlying celiac disease as well as potential novel disease biomarkers.
Cell Stress and Chaperones 03/2014; 19(6). DOI:10.1007/s12192-014-0507-6 · 3.16 Impact Factor
Available from: Minao Furumura
- "Among them, eTG, rather than tTG is considered as the domain autoantigen in DH . Recent studies reported a high sensitivity and specificity of eTG ELISA for DH  . In a few Japanese DH patients who were tested for DH-related autoantibodies, no autoantibodies except for IgA anti-eTG antibodies were detected. "
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ABSTRACT: We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. The mean age at onset was 43.8, and 13 years earlier for female patients. More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients.
Clinical and Developmental Immunology 06/2012; 2012(6):562168. DOI:10.1155/2012/562168 · 2.93 Impact Factor
Available from: Diletta Bonciani
- "Taken together, these data suggest that eTG rather than tTG seems to be the autoantigenic target in patients with DH, while tTG is the dominant antigen for CD. A study by Rose et al.  demonstrated that antibodies to eTG are the most sensitive serologic marker for the diagnosis of DH. In particular, a sensitivity of 95% was reported, confirming the study by Sardy et al. , in which the sensitivity was 92%, although Heil et al.  and Hull et al.  found anti-eTG antibodies in only 45% and 52% of patients with untreated DH, respectively. "
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ABSTRACT: Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.
Clinical and Developmental Immunology 06/2012; 2012(1):239691. DOI:10.1155/2012/239691 · 2.93 Impact Factor
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