TY - JOUR
T1 - A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen
AU - Landegren, Nils
AU - Ishii, Norito
AU - Aranda-Guillen, Maribel
AU - Gunnarsson, Horður Ingi
AU - Sardh, Fabian
AU - Hallgren, Åsa
AU - Ståhle, Mona
AU - Hagforsen, Eva
AU - Bradley, Maria
AU - Edqvist, Per Henrik D.
AU - Ponten, Fredrik
AU - Makitie, Outi
AU - Eidsmo, Liv
AU - Norlen, Lars
AU - Achour, Adnane
AU - Dahlbom, Ingrid
AU - Korponay-Szabo, Ilma
AU - Agardh, Daniel
AU - Alimohammadi, Mohammad
AU - Eriksson, Daniel
AU - Hashimoto, Takashi
AU - Kampe, Olle
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Autoantibodies
KW - Autoimmunity
KW - Biomarkers
KW - Paraneoplastic
KW - Transglutaminase
U2 - 10.1073/pnas.2100687118
DO - 10.1073/pnas.2100687118
M3 - Article
C2 - 34911754
AN - SCOPUS:85122558809
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
M1 - e2100687118
ER -
