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

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Landegren N, Ishii N, Aranda-Guillén M, Gunnarsson HI, Sardh F, Hallgren Å, Ståhle M, Hagforsen E, Bradley M, Edqvist PD, Pontén F, Mäkitie O, Eidsmo L, Norlén L, Achour A, Dahlbom I, Korponay-Szabó I, Agardh D, Alimohammadi M, Eriksson D, Hashimoto T, Kämpe O

Proc. Natl. Acad. Sci. U.S.A. 118 (51) - [2021-12-21; online 2021-12-17]

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.

PubMed 34911754

DOI 10.1073/pnas.2100687118

Crossref 10.1073/pnas.2100687118

pmc: PMC8713791
pii: 2100687118