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Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

by Genge, Palak C , Graybuck, Lucas T , Heubeck, Alexander T , LaFrance, Christian M , Gustafson, Claire E , Stuckey, Tyanna J , Kuan, Emma L , Trieu, Nguyen , Arishi, Najeeb A , Siedschlag, Marguerite D , Firestein, Gary S , Roll, Charles R , Deane, Kevin D , Collora, Christopher E , Zaim, Samir Rachid , Dornisch, Elisabeth M , He, Ziyuan , Venkatesan, Pravina , Swanson, Elliott G , Asamoah, Ashley G , Criley, Megan A L , Musgrove, Blessing , Li, Xiao-Jun , Mettey, Regina R , Peng, Tao , Moss, LauraKay , Feser, Marie L , Reading, Julian , Tran, Nhung T T , Fleischer, Chelsie L , Nguyen, Kathryn , Li, Ruoxin , Zhang, Fan , Barzideh, Saman , Gillespie, Mark A , Boyle, David L , Glass, Marla C , Lee, Kevin J , Pedrick, Chong , Hattel, Brian C , Wang, Wei , Ochoa, Andrea , Garber, Jessica , Pebworth, Mark-Phillip , Westermann, Amy , Weiss, Morgan D A , Krishnan, Upaasana , Okada, Lauren Y , Lord, Cara , Hernandez, Veronica , Striebich, Christopher C , Buckner, Jane H , Ravisankar, Padmapriyadarshini , Demoruelle, M Kristen , Phalen, Cole G , Bennett, Christy E , Gong, Qiuyu , Kawelo, Erin K , Bumol, Thomas F , Torgerson, Troy R , He, Yudong D , Holers, V Michael , Becker, L

in Immunology

2024

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Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

in Immunology

2024

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Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

in Immunology

2024

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Journal Article

Systemic inflammation and lymphocyte activation precede rheumatoid arthritis

Genge, Palak C,

Graybuck, Lucas T,

Heubeck, Alexander T,

LaFrance, Christian M,

Gustafson, Claire E,

Stuckey, Tyanna J,

Kuan, Emma L,

Trieu, Nguyen,

Arishi, Najeeb A,

Siedschlag, Marguerite D,

Firestein, Gary S,

Roll, Charles R,

Deane, Kevin D,

Collora, Christopher E,

Zaim, Samir Rachid,

Dornisch, Elisabeth M,

He, Ziyuan,

Venkatesan, Pravina,

Swanson, Elliott G,

Asamoah, Ashley G,

Criley, Megan A L,

Musgrove, Blessing,

Li, Xiao-Jun,

Mettey, Regina R,

Peng, Tao,

Moss, LauraKay,

Feser, Marie L,

Reading, Julian,

Tran, Nhung T T,

Fleischer, Chelsie L,

Nguyen, Kathryn,

Li, Ruoxin,

Zhang, Fan,

Barzideh, Saman,

Gillespie, Mark A,

Boyle, David L,

Glass, Marla C,

Lee, Kevin J,

Pedrick, Chong,

Hattel, Brian C,

Wang, Wei,

Ochoa, Andrea,

Garber, Jessica,

Pebworth, Mark-Phillip,

Westermann, Amy,

Weiss, Morgan D A,

Krishnan, Upaasana,

Okada, Lauren Y,

Lord, Cara,

Hernandez, Veronica,

Striebich, Christopher C,

Buckner, Jane H,

Ravisankar, Padmapriyadarshini,

Demoruelle, M Kristen,

Phalen, Cole G,

Bennett, Christy E,

Gong, Qiuyu,

Kawelo, Erin K,

Bumol, Thomas F,

Torgerson, Troy R,

He, Yudong D,

Holers, V Michael,

Becker, L

2024

Overview

Some autoimmune diseases, including rheumatoid arthritis (RA), are preceded by a critical subclinical phase of disease activity. Proactive clinical management is hampered by a lack of biological understanding of this subclinical 'at-risk' state and the changes underlying disease development. In a cross-sectional and longitudinal multi-omics study of peripheral immunity in the autoantibody-positive at-risk for RA period, we identified systemic inflammation, proinflammatory-skewed B cells, expanded Tfh17-like cells, epigenetic bias in naive T cells, TNF+IL1B+ monocytes resembling a synovial macrophage population, and CD4 T cell transcriptional features resembling those suppressed by abatacept (CTLA4-Ig) in RA patients. Our findings characterize pathogenesis prior to clinical diagnosis and suggest the at-risk state exhibits substantial immune alterations that could potentially be targeted for early intervention to delay or prevent autoimmunity. We provide a suite of tools at https://apps.allenimmunology.org/aifi/insights/ra-progression/ to facilitate exploration and enhance accessibility of this extensive dataset.

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Publisher

Cold Spring Harbor Laboratory

Subject

Immunology