Dermatitis Herpetiformis‐an Autoimmune Disease due to Cross‐Reaction between Dietary Glutenin and Dermal Elastin?

Abstract

Dermatitis herpetiformis (DH), is associated with skin eruptions and granular depositions of IgA in the papillary dermis, but this is not a feature of coeliac disease (CD). The specificity of the IgA in the skin is unknown. High molecular weight glutenin (HMW-g), a component of gluten, has been shown to have structural similarities to human elastin. This paper reports immunoadsorption studies which suggest that human serum may contain antibodies which cross-react with HMW-g and elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g and to elastin than both CD patients and healthy controls. Furthermore, introduction of a gluten-free diet (GFD) was associated with a further reduction in the amount of IgA antibodies to elastin in the DH patients. This diet-associated decrease of elastin antibodies was restricted to the IgA isotype. A significant correlation was observed between IgA antibodies to HMW-g and elastin in healthy controls and CD patients, while no such correlation was found in patients with DH. These findings could indicate that HMW-g induces production of antibodies to elastin, which are deposited in the skin, and that when the antigenic stimulus is removed, these antibodies are further reduced due to continuous dermal deposition. It is postulated that DH may be an autoimmune disease due to cross-reactivity between dietary glutenin and dermal elastin.

Fibrillar IgA deposition may be associated with atypical dermatitis herpetiformis – a report of two cases

“…It is well known that antibodies from DH sera do not bind to normal skin by indirect IMF and they comment that this is consistent with IgA binding to an abnormal or denatured component of the BMZ. A further theory for the pathogenesis of DH was proposed by Bodvarsson et al who found antibodies in human serum which cross-react with high molecular weight glutenin (HMW-g) -a component of gluten [8]. They showed that patients with DH had lower levels of IgA antibodies to HMW-g and elastin than patients with GSE or healthy controls.…”

Cross-Reaction between Gliadin and Different Food and Tissue Antigens

“…During the past decade, it has been well established that CD is associated with various extraintestinal autoimmunities that involve the thyroid, joints, heart, skin, pancreas, bone, liver, reproductive organs, and the nervous system [38][39][40][41][42][43][44][45][46][47]. Although the exact mechanisms for the induction of these autoimmunities are not definitively known, there is a growing body of evidence indicating that these diseases may result from molecular mimicry between gliadin or transglutaminase and various tissue antigens, including nervous system proteins [8,[41][42][43]48].…”

“…Interestingly, the celiac peptide VVKVGGSSSLGW shares more than 30% homology with the transglutaminase peptide 476-487 (RIRVGQSMNMGS) [8]. In earlier studies, it was established that antibodies against transglutaminase generated in the intestine can bind to extraintestinal tissues such as those of the liver, pancreas, lymph nodes, muscle, heart and brain [7,[44][45][46][48][49][50][51]. These studies demonstrated that the circulating antibodies present in celiac disease interact with ubiquitous transglutaminases in various tissues, which may induce the formation of protein aggregates that may trigger inflammation [48].…”

Celiac sprue: a unique autoimmune disorder

“…The two main autoantibodies are anti-tTG and anti-epidermal transglutaminase (TGe), with anti-TGe found in DH, and anti-tTG in CS and in most cases of DH. Elastin has also been suggested as a possible autoantigen in DH owing to the cross-reactivity between glutenin and dermal elastin [39]. As such, these antibodies are clearly directed against self-proteins and can be considered an autoimmune feature of both CS and DH.…”