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Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis.

Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N - J. Exp. Med. (2002)

Bottom Line: Gluten sensitivity typically presents as celiac disease, a common chronic small intestinal disorder.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.Further, these patients have an antibody population specific for this enzyme.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermato-Venereology, Semmelweis University, H-1085 Budapest, Mária u.41, Hungary. sardy@bor.sote.hu

ABSTRACT
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.

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Transglutaminase inhibition ELISAs, typical examples of inhibition curves. Each diagram shows the effect of preincubation on the remaining IgA Ab reactivity in one single serum sample from a patient with untreated CD (A and C) or DH (B and D). On the vertical axis is the remaining IgA Ab reactivity against TGc (A and B) or TGe (C and D) given in percentage of the buffer control, on the horizontal axis are inhibitor amounts on a logarithmic scale used for preincubation. The control was preincubated with buffer only, the other samples with a serial dilution of TGc (continuous line) or TGe (dashed line). The TGe is seen to be an effective inhibitor of IgA Abs against TGe only in DH patients (D), but not in individuals with CD (C) (see group analysis in Fig. 4, statistics in the text). TGc has the greatest inhibitory effect on IgA Abs against TGc in CD patients (A).
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fig3: Transglutaminase inhibition ELISAs, typical examples of inhibition curves. Each diagram shows the effect of preincubation on the remaining IgA Ab reactivity in one single serum sample from a patient with untreated CD (A and C) or DH (B and D). On the vertical axis is the remaining IgA Ab reactivity against TGc (A and B) or TGe (C and D) given in percentage of the buffer control, on the horizontal axis are inhibitor amounts on a logarithmic scale used for preincubation. The control was preincubated with buffer only, the other samples with a serial dilution of TGc (continuous line) or TGe (dashed line). The TGe is seen to be an effective inhibitor of IgA Abs against TGe only in DH patients (D), but not in individuals with CD (C) (see group analysis in Fig. 4, statistics in the text). TGc has the greatest inhibitory effect on IgA Abs against TGc in CD patients (A).

Mentions: To discover the significance of Ab cross-reactivity between these enzymes within the two patient groups, we performed inhibition studies. ELISA plates were coated with either human TGc or TGe, and the patient sera were preincubated with various concentrations of either of the two transglutaminases. Initial experiments allowed us to find appropriate serum dilutions giving results within a linear range for the given ELISA. The degree of inhibition produced by the preincubation with either of the two proteins was compared with control samples where the sera had been preincubated with buffer alone. The results are presented as reduction in the optical density given as percentage of the controls. Two examples of these inhibition ELISAs performed over a range of inhibitor concentrations with typical CD and DH sera are shown in Fig. 3. For group analysis of 36 CD and 34 DH patients, results of inhibition with 32 ng and 1 μg of the relevant transglutaminase are shown in Fig. 4.


Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis.

Sárdy M, Kárpáti S, Merkl B, Paulsson M, Smyth N - J. Exp. Med. (2002)

Transglutaminase inhibition ELISAs, typical examples of inhibition curves. Each diagram shows the effect of preincubation on the remaining IgA Ab reactivity in one single serum sample from a patient with untreated CD (A and C) or DH (B and D). On the vertical axis is the remaining IgA Ab reactivity against TGc (A and B) or TGe (C and D) given in percentage of the buffer control, on the horizontal axis are inhibitor amounts on a logarithmic scale used for preincubation. The control was preincubated with buffer only, the other samples with a serial dilution of TGc (continuous line) or TGe (dashed line). The TGe is seen to be an effective inhibitor of IgA Abs against TGe only in DH patients (D), but not in individuals with CD (C) (see group analysis in Fig. 4, statistics in the text). TGc has the greatest inhibitory effect on IgA Abs against TGc in CD patients (A).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2193738&req=5

fig3: Transglutaminase inhibition ELISAs, typical examples of inhibition curves. Each diagram shows the effect of preincubation on the remaining IgA Ab reactivity in one single serum sample from a patient with untreated CD (A and C) or DH (B and D). On the vertical axis is the remaining IgA Ab reactivity against TGc (A and B) or TGe (C and D) given in percentage of the buffer control, on the horizontal axis are inhibitor amounts on a logarithmic scale used for preincubation. The control was preincubated with buffer only, the other samples with a serial dilution of TGc (continuous line) or TGe (dashed line). The TGe is seen to be an effective inhibitor of IgA Abs against TGe only in DH patients (D), but not in individuals with CD (C) (see group analysis in Fig. 4, statistics in the text). TGc has the greatest inhibitory effect on IgA Abs against TGc in CD patients (A).
Mentions: To discover the significance of Ab cross-reactivity between these enzymes within the two patient groups, we performed inhibition studies. ELISA plates were coated with either human TGc or TGe, and the patient sera were preincubated with various concentrations of either of the two transglutaminases. Initial experiments allowed us to find appropriate serum dilutions giving results within a linear range for the given ELISA. The degree of inhibition produced by the preincubation with either of the two proteins was compared with control samples where the sera had been preincubated with buffer alone. The results are presented as reduction in the optical density given as percentage of the controls. Two examples of these inhibition ELISAs performed over a range of inhibitor concentrations with typical CD and DH sera are shown in Fig. 3. For group analysis of 36 CD and 34 DH patients, results of inhibition with 32 ng and 1 μg of the relevant transglutaminase are shown in Fig. 4.

Bottom Line: Gluten sensitivity typically presents as celiac disease, a common chronic small intestinal disorder.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.Further, these patients have an antibody population specific for this enzyme.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermato-Venereology, Semmelweis University, H-1085 Budapest, Mária u.41, Hungary. sardy@bor.sote.hu

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus