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Adult-Onset Anti-Ci...
Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+T Lymphocyte Signature
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- Kelkka, Tiina (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Savola, Paula (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Bhattacharya, Dipabarna (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Huuhtanen, Jani (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Lonnberg, Tapio (författare)
- Univ Turku, Finland; Abo Akad Univ, Finland
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- Kankainen, Matti (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Paalanen, Kirsi (författare)
- Jyvaskyla Cent Hosp, Finland
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- Tyster, Mikko (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Lepisto, Maija (författare)
- Univ Helsinki, Finland
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- Ellonen, Pekka (författare)
- Univ Helsinki, Finland
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- Smolander, Johannes (författare)
- Univ Turku, Finland; Abo Akad Univ, Finland
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- Eldfors, Samuli (författare)
- Univ Helsinki, Finland
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- Yadav, Bhagwan (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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- Khan, Sofia (författare)
- Univ Turku, Finland; Abo Akad Univ, Finland
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- Koivuniemi, Riitta (författare)
- Univ Helsinki, Finland
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- Sjöwall, Christopher (författare)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Elo, Laura L. (författare)
- Univ Turku, Finland; Abo Akad Univ, Finland
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- Lahdesmaki, Harri (författare)
- Aalto Univ, Finland
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- Maeda, Yuka (författare)
- Natl Canc Ctr, Japan
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- Nishikawa, Hiroyashi (författare)
- Natl Canc Ctr, Japan
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- Leirisalo-Repo, Marjatta (författare)
- Univ Helsinki, Finland
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- Sokka-Isler, Tuulikki (författare)
- Jyvaskyla Cent Hosp, Finland; Univ Eastern Finland, Finland
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- Mustjoki, Satu (författare)
- Univ Helsinki, Finland; Helsinki Univ Hosp, Finland
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(creator_code:org_t)
- 2020-11-19
- 2020
- Engelska.
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 11
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://www.frontier...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Rheumatoid arthritis (RA) is a complex autoimmune disease targeting synovial joints. Traditionally, RA is divided into seropositive (SP) and seronegative (SN) disease forms, the latter consisting of an array of unrelated diseases with joint involvement. Recently, we described a severe form of SN-RA that associates with characteristic joint destruction. Here, we sought biological characteristics to differentiate this rare but aggressive anti-citrullinated peptide antibody-negative destructive RA (CND-RA) from early seropositive (SP-RA) and seronegative rheumatoid arthritis (SN-RA). We also aimed to study cytotoxic CD8+ lymphocytes in autoimmune arthritis. CND-RA, SP-RA and SN-RA were compared to healthy controls to reveal differences in T-cell receptor beta (TCR beta) repertoire, cytokine levels and autoantibody repertoires. Whole-exome sequencing (WES) followed by single-cell RNA-sequencing (sc-RNA-seq) was performed to study somatic mutations in a clonally expanded CD8+ lymphocyte population in an index patient. A unique TCR beta signature was detected in CND-RA patients. In addition, CND-RA patients expressed higher levels of the bone destruction-associated TNFSF14 cytokine. Blood IgG repertoire from CND-RA patients recognized fewer endogenous proteins than SP-RA patients repertoires. Using WES, we detected a stable mutation profile in the clonally expanded CD8+ T-cell population characterized by cytotoxic gene expression signature discovered by sc-RNA-sequencing. Our results identify CND-RA as an independent RA subset and reveal a CND-RA specific TCR signature in the CD8+ lymphocytes. Improved classification of seronegative RA patients underlines the heterogeneity of RA and also, facilitates development of improved therapeutic options for the treatment resistant patients.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- rheumatoid arthritis; seronegative; ACPA-negative; CD8+lymphocyte; T cell receptor; somatic mutation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Kelkka, Tiina
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Savola, Paula
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Bhattacharya, Di ...
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Huuhtanen, Jani
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Lonnberg, Tapio
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Kankainen, Matti
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visa fler...
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Paalanen, Kirsi
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Tyster, Mikko
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Lepisto, Maija
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Ellonen, Pekka
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Smolander, Johan ...
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Eldfors, Samuli
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Yadav, Bhagwan
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Khan, Sofia
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Koivuniemi, Riit ...
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Sjöwall, Christo ...
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Elo, Laura L.
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Lahdesmaki, Harr ...
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Maeda, Yuka
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Nishikawa, Hiroy ...
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Leirisalo-Repo, ...
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Sokka-Isler, Tuu ...
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Mustjoki, Satu
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