Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis

Hull, Christopher M.; Liddle, M.; Hansen, Nana Wesley; Meyer, Laurence; Schmidt, Linda; Taylor, Tomaro; Jaskowski, Troy D.; Hill, Harry R.; Zone, John J.

doi:10.1111/j.1365-2133.2008.08629.x

Cited by 83 publications

(72 citation statements)

References 18 publications

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“…Eleven DH cases had the level of serum IgA antibodies to TG3 above the manufacturer's cut-off value (52.4%); range of levels was 4.79-176.52 AU/ml. The low percentage of DH cases with elevated levels of serum IgA antibodies to TG3 in this study should not be considered unusual since in a recently published investigation only 52% of DH patients were shown to have those levels elevated [12]. It is known that dapsone impairs the functions of neutrophils, but our results were not influenced by this drug as none of patients was treated with dapsone prior to the establishment of the diagnosis of DH.…”

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confidence: 32%

Low Strength of Correlation between the Intensity of Neutrophil Elastase Expression in Lesional Skin and the Level of Serum IgA Antibodies to Epidermal Transglutaminase in Dermatitis Herpetiformis

Bowszyc‐Dmochowska¹,

Seraszek²,

Kaczmarek³

et al. 2009

TOAUTOJ

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Abstract:Whereas it has been shown that neutrophil elastase (NE) is a crucial enzyme degrading the dermal-epidermal junction (DEJ) in bullous pemphigoid (BP), experimental studies on the role of NE in dermatitis herpetiformis (DH), a disease in which, as in BP, an intra-lamina lucida blister is formed, are scanty. The aim of this study was to analyse whether there is a correlation between levels of serum IgA antibodies to the epidermal transglutaminase (TG3), an enzyme believed to be the autoantigen of DH, and expression of NE in lesional skin in DH. A series of 21 consecutive patients with DH was studied. The levels of IgA antibodies to TG3 in sera were calculated with ELISA. The expressions of NE were examined with immunohistochemical technique in sections of lesional skin using a mouse monoclonal antibody to human NE. The digital microscopic image analysis with the appropriate software was then used to measure intensities of NE expression. The correlation between the intensity of NE expression in lesional skin and the level of serum IgA antibodies to TG3 in DH was of low strength. Thus, it is speculated that in DH the engagement of IgA autoantibodies to the enzyme, TG3, on cutaneous neutrophils might not be a principal stimulus to releasing NE, the enzyme known to degrade DEJ in subepidermal blistering diseases with autoimmunity to DEJ structural proteins. REPORTThe plausible pathophysiology of dermatitis herpetifomis (DH) is that the Fc region of IgA autoantibody to epidermal transglutaminase (TG3), an enzyme believed to be the most disease-specific autoantigen of DH, [1] activates neutrophils by engaging their CD89 receptor which leads to the release of neutrophil elastase (NE), NE-mediated destruction of the dermal-epidermal junction (DEJ) and the formation of an intra-lamina lucida blister. Whereas it was shown that NE is crucial DEJ-degrading enzyme in bullous pemphigoid (BP), [2][3] experimental studies on the role of NE in DH are scanty. Early data suggested that in blister fluids in patients with DH an activity of elastase, probably NE, can be detected [4][5]. The aim of this study was to analyse whether there is a correlation between levels of serum IgA antibodies to TG3 and expression of NE in lesional skin in DH.NE deposits and IgA antibodies to TG3 were evaluated in a series of 21 consecutive dapsone-untreated patients with DH, regardless whether they had concomitant intestinal problems or not. The diagnosis of DH in each case was made when whichever pattern of possible 7 diagnostic patterns of granular IgA deposition was detected with direct immunofluorescence of nonlesional skin [6][7][8]. The levels of IgA antibodies to TG3 in sera were calculated with ELISA in AU/ml (manufacturer's cut-off value 18AU/ml) (Immundiagnostic, Germany). The expressions of NE were examined with immunohistochemical technique in sections of lesional *Address correspondence to this author at the Department of Dermatology, University School of Medicine, Pozna , Poland; E-mail: dmoch@sylaba.poznan.pl skin showing histolo...

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confidence: 32%

Low Strength of Correlation between the Intensity of Neutrophil Elastase Expression in Lesional Skin and the Level of Serum IgA Antibodies to Epidermal Transglutaminase in Dermatitis Herpetiformis

Bowszyc‐Dmochowska¹,

Seraszek²,

Kaczmarek³

et al. 2009

TOAUTOJ

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“…It frequently is manifest in childhood, although it can first become symptomatic at any time in life. IgA Abs to TG2 have become the serologic hallmark and a diagnostic criterion for celiac disease and develop early in the course (23). They are thought to develop from an immune response to TG2, which plays an essential role in metabolizing the gliadin Ag.…”

Section: Discussionmentioning

confidence: 99%

Dermatitis Herpetiformis Sera or Goat Anti–Transglutaminase-3 Transferred to Human Skin-Grafted Mice Mimics Dermatitis Herpetiformis Immunopathology

Zone

Schmidt

Taylor

et al. 2011

The Journal of Immunology

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Dermatitis herpetiformis (DH) is characterized by deposition of IgA in the papillary dermis. However, indirect immunofluorescence is routinely negative, raising the question of the mechanism of formation of these immune deposits. Sárdy et al. (2002. J. Exp. Med. 195: 747–757) reported that transglutaminase-3 (TG3) colocalizes with the IgA. We sought to create such deposits using passive transfer of Ab to SCID mice bearing human skin grafts. IgG fraction of goat anti-TG3 or control IgG were administered i.p. to 20 mice. Separately, sera from seven DH patients and seven controls were injected intradermally. Biopsies were removed and processed for routine histology as well as direct immunofluorescence. All mice that received goat anti-TG3 produced papillary dermal immune deposits, and these deposits reacted with both rabbit anti-TG3 and DH patient sera. Three DH sera high in IgA anti-TG3 also produced deposits of granular IgA and TG3. We hypothesize that the IgA class anti-TG3 Abs are directly responsible for the immune deposits and that the TG3 is from human epidermis, as this is its only source in our model. These deposits seem to form over weeks in a process similar to an Ouchterlony immunodiffusion precipitate. This process of deposition explains the negative indirect immunofluorescence results with DH serum.

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“…Several studies showed that the ETG, rather than the TTG is the dominant autoantigen in DH [12,13]. This difference in autoantigens may be the reason for the different clinical presentation seen in DH and CD, which are thought to share same pathogenetic background.…”

Section: Discussionmentioning

confidence: 93%

Celiac disease of the joint

2010

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A 42-year-old woman presented with a 3-week history of left knee pain and swelling. She had suffered dermatitis herpetiformis for 12 years, proved by skin biopsy. She had never been on gluten-free diet. Knee pain increased with motion and her gait was antalgic. On admission, she was mainly dependent on wheelchair due to pain and limitation. Treatment plan consisted of gluten-free diet, stretching and strengthening exercises, analgesic or nonsteroidal anti-inflammatory drugs when needed. She responded well to gluten-free diet. Association of joint involvement and dermatitis herpetiformis is more than just coincidental. Possible immunopathogenesis and role of gluten-free diet on arthritis treatment are discussed.

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Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis

Abstract: IgA antibodies to TG3 are elevated in patients with DH and adults with CD. The progressive expansion of the epitope-binding profile of IgA antitransglutaminase antibodies in patients with CD may explain the development of DH in patients with undiagnosed CD during their adult life.

Cited by 83 publications

References 18 publications

Low Strength of Correlation between the Intensity of Neutrophil Elastase Expression in Lesional Skin and the Level of Serum IgA Antibodies to Epidermal Transglutaminase in Dermatitis Herpetiformis

Low Strength of Correlation between the Intensity of Neutrophil Elastase Expression in Lesional Skin and the Level of Serum IgA Antibodies to Epidermal Transglutaminase in Dermatitis Herpetiformis

Dermatitis Herpetiformis Sera or Goat Anti–Transglutaminase-3 Transferred to Human Skin-Grafted Mice Mimics Dermatitis Herpetiformis Immunopathology

Celiac disease of the joint

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