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

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

doi:10.1073/pnas.2100687118

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

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 ErikssonTakashi Hashimoto, Olle Kämpe

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

8 Citationer (Scopus)

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% 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.

Originalsprog	Engelsk
Tidsskrift	Proceedings of the National Academy of Sciences of the United States of America
Vol/bind	118
Udgave nummer	51
ISSN	0027-8424
DOI	https://doi.org/10.1073/pnas.2100687118
Status	Udgivet - 21 dec. 2021
Udgivet eksternt	Ja

Bibliografisk note

Adgang til dokumentet

10.1073/pnas.2100687118

Citationsformater

Landegren, N., Ishii, N., Aranda-Guillén, M., Gunnarsson, H. I., Sardh, F., Hallgren, Å., Ståhle, M., Hagforsen, E., Bradley, M., Edqvist, P.-H. D., Pontén, F., Mäkitie, O., Eidsmo, L., Norlén, L., Achour, A., Dahlbom, I., Korponay-Szabó, I., Agardh, D., Alimohammadi, M., ... Kämpe, O. (2021). A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen. Proceedings of the National Academy of Sciences of the United States of America, 118(51). https://doi.org/10.1073/pnas.2100687118

A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen. / Landegren, Nils; Ishii, Norito; Aranda-Guillén, Maribel et al.
I: Proceedings of the National Academy of Sciences of the United States of America, Bind 118, Nr. 51, 21.12.2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Landegren, N, Ishii, N, Aranda-Guillén, M, Gunnarsson, HI, Sardh, F, Hallgren, Å, Ståhle, M, Hagforsen, E, Bradley, M, Edqvist, P-HD, 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 2021, 'A gene-centric approach to biomarker discovery identifies transglutaminase 1 as an epidermal autoantigen', Proceedings of the National Academy of Sciences of the United States of America, bind 118, nr. 51. https://doi.org/10.1073/pnas.2100687118

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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% 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.",

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AU - Landegren, Nils

AU - Ishii, Norito

AU - Aranda-Guillén, Maribel

AU - Gunnarsson, Hörður Ingi

AU - Sardh, Fabian

AU - Hallgren, Åsa

AU - Ståhle, Mona

AU - Hagforsen, Eva

AU - Bradley, Maria

AU - Edqvist, Per-Henrik D

AU - Pontén, Fredrik

AU - Mäkitie, Outi

AU - Eidsmo, Liv

AU - Norlén, Lars

AU - Achour, Adnane

AU - Dahlbom, Ingrid

AU - Korponay-Szabó, Ilma

AU - Agardh, Daniel

AU - Alimohammadi, Mohammad

AU - Eriksson, Daniel

AU - Hashimoto, Takashi

AU - Kämpe, Olle

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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.

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KW - Case-Control Studies

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KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Paraneoplastic Syndromes/blood

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KW - Transglutaminases/immunology

KW - Young Adult

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DO - 10.1073/pnas.2100687118

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