{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:50:00Z","timestamp":1788997800425,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T00:00:00Z","timestamp":1581552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Foundation for Paediatric Research","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"The Research Fund of the Finnish Coeliac Society","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"the Competitive State Research Financing of the Expert Area of Tampere University Hospital","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.<\/jats:p>","DOI":"10.3390\/nu12020467","type":"journal-article","created":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T10:09:57Z","timestamp":1581674997000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge"],"prefix":"10.3390","volume":"12","author":[{"given":"Hanna","family":"Sankari","sequence":"first","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Hietikko","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Kurppa","sequence":"additional","affiliation":[{"name":"Tampere Center for Child Health Research, Tampere University, Tampere, the Department of Paediatrics, Tampere University Hospital, 33520 Tampere, Finland"},{"name":"The University Consortium of Sein\u00e4joki and Sein\u00e4joki Central Hospital, 60220 Sein\u00e4joki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Kaukinen","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"},{"name":"Department of Internal Medicine, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriika","family":"Mansikka","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"},{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1372-430X","authenticated-orcid":false,"given":"Heini","family":"Huhtala","sequence":"additional","affiliation":[{"name":"Faculty of Social Sciences, Tampere University, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaija","family":"Laurila","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Reunala","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaisa","family":"Hervonen","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"},{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teea","family":"Salmi","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"},{"name":"Department of Dermatology, Tampere University Hospital, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-5151","authenticated-orcid":false,"given":"Katri","family":"Lindfors","sequence":"additional","affiliation":[{"name":"Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1084\/jem.20011299","article-title":"Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis","volume":"195","author":"Sardy","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/j.1365-2133.2008.08629.x","article-title":"Elevation of IgA anti-epidermal transglutaminase antibodies in dermatitis herpetiformis","volume":"159","author":"Hull","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.dld.2016.03.003","article-title":"Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis","volume":"48","author":"Salmi","year":"2016","journal-title":"Dig. Liver Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/sj.jid.5701041","article-title":"Transglutaminase autoantibodies in dermatitis herpetiformis and celiac sprue","volume":"128","author":"Marietta","year":"2008","journal-title":"J. Investig Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1111\/j.1365-2133.2003.05579.x","article-title":"Long-term remission in patients with dermatitis herpetiformis on a normal diet","volume":"149","author":"Bardella","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/bjd.15995","article-title":"Disappearance of epidermal transglutaminase and IgA deposits from the papillary dermis of dermatitis herpetiformis patients after a long-term gluten-free diet","volume":"178","author":"Hietikko","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jaad.2008.12.037","article-title":"Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet","volume":"61","author":"Rose","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1111\/bjd.13387","article-title":"IgA antiepidermal transglutaminase antibodies in dermatitis herpetiformis: A significant but not complete response to a gluten-free diet treatment","volume":"17","author":"Reunala","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/j.jid.2019.03.1150","article-title":"Gluten challenge induces skin and small bowel relapse in long-term gluten-free diet-treated dermatitis herpetiformis","volume":"139","author":"Mansikka","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1136\/gut.32.5.487","article-title":"HLA association with dermatitis herpetiformis is accounted for by a cis or transassociated DQ heterodimer","volume":"32","author":"Hall","year":"1991","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1136\/gut.25.2.151","article-title":"Dermatitis herpetiformis: Diagnosis, diet and demography","volume":"25","author":"Gawkrodger","year":"1984","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1136\/adc.59.6.517","article-title":"Dermatitis herpetiformis: Jejunal findings and skin response to gluten free diet","volume":"59","author":"Reunala","year":"1984","journal-title":"Arch. Dis. Child."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1136\/gut.33.2.206","article-title":"Increase of lymphocytes bearing the gamma\/delta T cell receptor in the jejunum of patients with dermatitis herpetiformis","volume":"33","author":"Savilahti","year":"1992","journal-title":"Gut"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1111\/j.1572-0241.2003.07456.x","article-title":"Intraepithelial lymphocytes in celiac disease","volume":"98","author":"Kaukinen","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nm0797-797","article-title":"Identification of tissue transglutaminase as the autoantigen of celiac disease","volume":"3","author":"Dieterich","year":"1997","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/gut.2003.024836","article-title":"In vivo targeting of intestinal and extraintestinal transglutaminase 2 by coeliac autoantibodies","volume":"53","author":"Halttunen","year":"2004","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1046\/j.1523-1747.1999.00627.x","article-title":"Antibodies to tissue transglutaminase as serologic markers in patients with dermatitis herpetiformis","volume":"113","author":"Dieterich","year":"1999","journal-title":"J. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2340\/00015555-1764","article-title":"Small bowel transglutaminase 2-specific IgA deposits in dermatitis herpetiformis","volume":"94","author":"Salmi","year":"2014","journal-title":"Acta Derm. Venereol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/mi.2015.57","article-title":"Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease","volume":"9","author":"Snir","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nm.2656","article-title":"High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions","volume":"18","author":"Mesin","year":"2012","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hietikko, M., Koskinen, O., Kurppa, K., Laurila, K., Saavalainen, P., Salmi, T., Ilus, T., Huhtala, H., Kaukinen, K., and Lindfors, K. (2018). Small-intestinal TG2-specific plasma cells at different stages of coeliac disease. BMC Immunol., 19.","DOI":"10.1186\/s12865-018-0275-7"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"366","DOI":"10.2340\/00015555-2849","article-title":"Ex vivo culture of duodenal biopsies from patients with Dermatitis herpetiformis indicates that transglutaminase 3 antibody production occurs in the gut","volume":"98","author":"Hietikko","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/00365529850170810","article-title":"IgA- and IgG-class antihuman umbilical cord antibody tests in adult coeliac disease","volume":"33","author":"Sulkanen","year":"1998","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Taavela, J., Koskinen, O., Huhtala, H., L\u00e4hdeaho, M.L., Popp, A., Laurila, K., Collin, P., Kaukinen, K., Kurppa, K., and M\u00e4ki, M. (2013). Validation of morphometric analyses of small-intestinal biopsy readouts in celiac disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076163"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/07853890.2016.1222450","article-title":"Dermatitis herpetiformis: A cutaneous manifestation of coeliac disease","volume":"49","author":"Collin","year":"2017","journal-title":"Ann. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1053\/j.gastro.2018.12.013","article-title":"Plasma Cells are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease","volume":"156","author":"Richter","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1016\/j.celrep.2017.08.036","article-title":"Strong Clonal Relatedness between Serum and Gut IgA despite Different Plasma Cell Origins","volume":"20","author":"Iversen","year":"2017","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5981","DOI":"10.4049\/jimmunol.1300183","article-title":"Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells","volume":"190","author":"Iversen","year":"2013","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1001\/archderm.1986.01660160074022","article-title":"Dermatitis herpetiformis: Cutaneous deposition of polyclonal IgA1","volume":"122","author":"Olbricht","year":"1986","journal-title":"Arch. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1159\/000234516","article-title":"Identification of IgA subclasses in skin of dermatitis herpetiformis patients","volume":"85","author":"Barghuthy","year":"1988","journal-title":"Int. Arch. Allergy Immunol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/2\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:57:19Z","timestamp":1760173039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/2\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,13]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["nu12020467"],"URL":"https:\/\/doi.org\/10.3390\/nu12020467","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,13]]}}}