A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen

Landegren, NilsKarolinska Institutet,Uppsala University,Karolinska Institute (author)

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.

Ishii, Norito (author)
Aranda-Guillen, MaribelKarolinska Institutet,Karolinska Institute (author)
Gunnarsson, Horður IngiKarolinska Institute (author)
Sardh, FabianKarolinska Institute (author)
Hallgren, ÅsaKarolinska Institute (author)
Ståhle, MonaKarolinska Institutet (author)
Hagforsen, EvaUppsala University (author)
Bradley, MariaKarolinska Institutet (author)
Edqvist, Per Henrik D.Uppsala University (author)
Ponten, FredrikUppsala University (author)
Makitie, OutiKarolinska Institutet,Karolinska Institute,Karolinska University Hospital,Folkhälsan Research Center (author)
Eidsmo, LivKarolinska Institutet (author)
Norlen, LarsKarolinska Institutet,Karolinska Institute,Karolinska University Hospital (author)
Achour, AdnaneKarolinska Institutet,Karolinska Institute,Karolinska University Hospital (author)
Dahlbom, IngridUppsala University (author)
Korponay-Szabo, IlmaUniversity of Debrecen (author)
Agardh, DanielLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups(Swepub:lu)med-dia (author)
Alimohammadi, MohammadUppsala University (author)
Eriksson, DanielKarolinska Institutet,Karolinska Institute,Karolinska University Hospital (author)
Hashimoto, Takashi (author)
Kampe, OlleKarolinska Institutet,Karolinska Institute,Karolinska University Hospital,University of Bergen (author)
Uppsala UniversityKarolinska Institute (creator_code:org_t)

In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences118:510027-84241091-6490
In:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences118:511091-6490

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Dermatology and ...

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