A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen
(2021) In Proceedings of the National Academy of Sciences of the United States of America 118(51).- Abstract
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%... (More)
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.
(Less)
- author
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Autoantibodies, Autoimmunity, Biomarkers, Paraneoplastic, Transglutaminase
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 118
- issue
- 51
- article number
- e2100687118
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:34911754
- scopus:85122558809
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.2100687118
- language
- English
- LU publication?
- yes
- id
- ce9c84e1-7584-4b3e-96d8-410beca18acd
- date added to LUP
- 2022-03-10 12:38:03
- date last changed
- 2024-06-13 11:25:42
@article{ce9c84e1-7584-4b3e-96d8-410beca18acd, abstract = {{<p>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.</p>}}, author = {{Landegren, Nils and Ishii, Norito and Aranda-Guillen, Maribel and Gunnarsson, Horður Ingi and Sardh, Fabian and Hallgren, Åsa and Ståhle, Mona and Hagforsen, Eva and Bradley, Maria and Edqvist, Per Henrik D. and Ponten, Fredrik and Makitie, Outi and Eidsmo, Liv and Norlen, Lars and Achour, Adnane and Dahlbom, Ingrid and Korponay-Szabo, Ilma and Agardh, Daniel and Alimohammadi, Mohammad and Eriksson, Daniel and Hashimoto, Takashi and Kampe, Olle}}, issn = {{0027-8424}}, keywords = {{Autoantibodies; Autoimmunity; Biomarkers; Paraneoplastic; Transglutaminase}}, language = {{eng}}, number = {{51}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences of the United States of America}}, title = {{A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen}}, url = {{http://dx.doi.org/10.1073/pnas.2100687118}}, doi = {{10.1073/pnas.2100687118}}, volume = {{118}}, year = {{2021}}, }