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TG6 auto-antibodies in dermatitis herpetiformis

Hadjivassiliou, M., Reunala, T., Hervonen, K., Aeschlimann, P. and Aeschlimann, D. 2020. TG6 auto-antibodies in dermatitis herpetiformis. Nutrients 12 (9) , 2884. 10.3390/nu12092884

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Dermatitis Herpetiformis (DH) is an extraintestinal manifestation of gluten sensitivity in which an autoimmune response is directed against transglutaminase 3 (TG3), an epidermal transglutaminase. TG2 is the autoantigen in coeliac disease (CD) defined by the presence of enteropathy and TG6 the autoantigen in neurological manifestations of gluten sensitivity. The interplay between B cell responses to these 3 transglutaminases in developing the clinical spectrum of disease manifestations remains incompletely understood, and individual or combined diagnostic and predictive value of respective autoantibodies has not been fully explored. We examined the prevalence of TG6 antibodies in a cohort of patients with DH. TG6 positivity was found in 13/33 (39%), with IgA detected in 11 patients, IgG in 3, and both in 1. This is significantly higher to what is seen in classic CD cases (14%) in the Finnish population. TG6 positive baseline samples constituted 60% of patients with DH with no enteropathy (n=10) as opposed to 17% positivity in those with overt enteropathy (n=12; Marsh IIIB). Repeat testing after adherence to a gluten free diet for 1 year showed reduced titres for TG6 antibodies in 11/13 (85%), whereby 7 patients were now TG6 antibody negative. Four patients seroconverted and tested positive for TG6 antibodies at one year due to ongoing exposure to gluten. We report another patient who presented with neurological manifestations (encephalopathy) leading to the diagnosis of CD who was intermittently adhering to a gluten free diet. Serological testing at baseline showed him to be positive for antibodies to all 3 transglutaminases. Eleven years later he developed DH. He also subsequently developed ataxia and peripheral neuropathy. Although TG3 and TG6 autoantibodies are linked to certain disease manifestations, TG2, TG3 and TG6 autoantibodies can be present across the spectrum of GRD patients and may develop years before onset of symptoms of extraintestinal manifestations. This is consistent with gluten-dependent adaptive immunity being a necessary but not sufficient pretext to organ-specific damage. TG6 antibodies appear to be developing more frequently in patients where tolerance to gluten has been broken but that either have not developed the molecular state driving tissue destruction at the level of the gut, or perhaps more likely are more resistant to developing this phenotype.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Dentistry
Publisher: MDPI
ISSN: 2072-6643
Date of First Compliant Deposit: 15 September 2020
Date of Acceptance: 15 September 2020
Last Modified: 22 Sep 2020 10:42

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