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Epidermal transglutaminase (TGase 3) Is the autoantigen of dermatitis herpetiformis

Epidermal transglutaminase (TGase 3) Is the autoantigen of dermatitis herpetiformis
Epidermal transglutaminase (TGase 3) Is the autoantigen of dermatitis herpetiformis
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.
gluten sensitive enteropathy, celiac disease, IgA, immune complex, skin
0022-1007
747-757
Sárdy, Miklós
f9049207-8012-4129-b2ff-11972ac8e697
Karpati, Sarolta
be29b7e4-59e0-47da-8ea3-b428b782a2cf
Merkl, Barbara
d2a911be-d3d6-4cd3-a1ba-91de810b9502
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Smyth, Neil
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Sárdy, Miklós
f9049207-8012-4129-b2ff-11972ac8e697
Karpati, Sarolta
be29b7e4-59e0-47da-8ea3-b428b782a2cf
Merkl, Barbara
d2a911be-d3d6-4cd3-a1ba-91de810b9502
Paulsson, Mats
6b6500dc-6e7c-477b-96be-8ebdf82224bf
Smyth, Neil
0eba2a40-3b43-4d40-bb64-621bd7e9d505

Sárdy, Miklós, Karpati, Sarolta, Merkl, Barbara, Paulsson, Mats and Smyth, Neil (2002) Epidermal transglutaminase (TGase 3) Is the autoantigen of dermatitis herpetiformis The Journal of Experimental Medicine, 195, (6), pp. 747-757. (doi:10.1084/jem.20011299).

Record type: Article

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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Published date: 18 March 2002
Keywords: gluten sensitive enteropathy, celiac disease, IgA, immune complex, skin

Identifiers

Local EPrints ID: 37532
URI: http://eprints.soton.ac.uk/id/eprint/37532
ISSN: 0022-1007
PURE UUID: f3c65533-6d48-42b2-a2c0-0d889efd58b2

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Date deposited: 25 May 2006
Last modified: 17 Jul 2017 15:42

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Contributors

Author: Miklós Sárdy
Author: Sarolta Karpati
Author: Barbara Merkl
Author: Mats Paulsson
Author: Neil Smyth

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