A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen
| العنوان: | A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen |
|---|---|
| المؤلفون: | Nils, Landegren, Norito, Ishii, Maribel, Aranda-Guillén, Hörður Ingi, Gunnarsson, Fabian, Sardh, Åsa, Hallgren, Mona, Ståhle, Eva, Hagforsen, Maria, Bradley, Per-Henrik D, Edqvist, Fredrik, Pontén, Outi, Mäkitie, Liv, Eidsmo, Lars, Norlén, Adnane, Achour, Ingrid, Dahlbom, Ilma, Korponay-Szabó, Daniel, Agardh, Mohammad, Alimohammadi, Daniel, Eriksson, Takashi, Hashimoto, Olle, Kämpe |
| المساهمون: | HUS Children and Adolescents, Clinicum, Lastentautien yksikkö, Children's Hospital, Department of Medical and Clinical Genetics |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America |
| بيانات النشر: | National Academy of Sciences, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Medical Sciences, Adolescent, Paraneoplastic Syndromes, autoantibodies, 腫瘍随伴性天疱瘡, Autoantigens, Young Adult, transglutaminase, 自己抗体探索システム, Humans, Child, トランスグルタミナーゼ, Aged, Aged, 80 and over, Transglutaminases, integumentary system, autoimmunity, 1184 Genetics, developmental biology, physiology, biomarkers, Middle Aged, Biological Sciences, Case-Control Studies, 3121 General medicine, internal medicine and other clinical medicine, paraneoplastic, Female, TGM1, Pemphigus |
| الوصف: | Significance The nine-member transglutaminase protein family includes five known autoantigens. Because of the frequent roles of transglutaminases in autoimmunity, we decided to explore whether the remaining members might also constitute autoantigens, but in as-yet-unexplained disorders. We turned to TGM1, and since this member is primarily expressed in squamous epithelia, we focused on skin disorders. By screening a broad range of acquired skin disorders, we identified TGM1 to be a major autoantigen in the severe blistering disease paraneoplastic pemphigus. This study illustrates a gene-centric approach to biomarker discovery—starting from a putative autoantigen to search for its corresponding disease—that may prove generally applicable for studies of autoimmunity. Autoantigen discovery is a critical challenge for the understanding and diagnosis of autoimmune diseases. While autoantibody markers in current clinical use have been identified through studies focused on individual disorders, we postulated that a reverse approach starting with a putative autoantigen to explore multiple disorders might hold promise. We here targeted the epidermal protein transglutaminase 1 (TGM1) as a member of a protein family prone to autoimmune attack. By screening sera from patients with various acquired skin disorders, we identified seropositive subjects with the blistering mucocutaneous disease paraneoplastic pemphigus. Validation in further subjects confirmed TGM1 autoantibodies as a 55% sensitive and 100% specific marker for paraneoplastic pemphigus. This gene-centric approach leverages the wealth of data available for human genes and may prove generally applicable for biomarker discovery in autoimmune diseases. |
| اللغة: | English |
| تدمد: | 1091-6490 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::cef4adf2ddf7a641e2986d6c5d4cb3cd https://dlisv03.media.osaka-cu.ac.jp/il/meta_pub/G0000438repository_10916490-118-51-e2100687118 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....cef4adf2ddf7a641e2986d6c5d4cb3cd |
| قاعدة البيانات: | OpenAIRE |
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