{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:14:41Z","timestamp":1774476881904,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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 celiac disease (CD), defined by the presence of enteropathy, and TG6 is 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 is not completely understood. Also, the individual or combined diagnostic and predictive value of the respective autoantibodies is not 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 was significantly higher compared to what is seen in the classic CD cases (14%) in a Finnish population. TG6 positive baseline samples constituted 60% of DH patients 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 titers 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 the 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 might 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 develop more frequently in patients where tolerance to gluten was broken but, either there was no development of the molecular state driving the tissue destruction at the level of the gut, or perhaps more likely, there was more resistance to developing this phenotype.<\/jats:p>","DOI":"10.3390\/nu12092884","type":"journal-article","created":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T21:01:21Z","timestamp":1600722081000},"page":"2884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["TG6 Auto-Antibodies in Dermatitis Herpetiformis"],"prefix":"10.3390","volume":"12","author":[{"given":"Marios","family":"Hadjivassiliou","sequence":"first","affiliation":[{"name":"Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust and University of Sheffield, Sheffield S10 2JF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Reunala","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"Celiac Disease Research Center, Tampere University and Faculty of Medicine and Health Technology, 33100 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-8399","authenticated-orcid":false,"given":"Kaisa","family":"Hervonen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"Celiac Disease Research Center, Tampere University and Faculty of Medicine and Health Technology, 33100 Tampere, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Aeschlimann","sequence":"additional","affiliation":[{"name":"Matrix Biology and Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0930-7706","authenticated-orcid":false,"given":"Daniel","family":"Aeschlimann","sequence":"additional","affiliation":[{"name":"Matrix Biology and Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Cardiff CF14 4XY, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sapone, A., Bai, J.C., Ciacci, C., Dolinsek, J., Green, P.H.R., Hadjivassiliou, M., Kaukinen, K., Rostami, K., Sanders, D.S., and Schumann, M. 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