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  • Kelkka, TiinaUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)

Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+T Lymphocyte Signature

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-11-19
  • FRONTIERS MEDIA SA,2020
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-172206
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-172206URI
  • https://doi.org/10.3389/fimmu.2020.578848DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|European Research CouncilEuropean Research Council (ERC) [M-IMM 647355, STRATIFY 862011, DynaOmics 677943]; Academy of Finland Heal-Art consortium [314442]; ERA PerMed (JAKSTAT-TARGET consortium); Finnish Medical foundation; Instrumentarium Science foundation; Biomedicum Helsinki foundation; Orion research foundation; Juhani Aho foundation; K. Albin Johansson foundation; Paulo foundation; Region Ostergotland (ALF grants); European UnionEuropean Union (EU) [675395]; Tekes the Finnish Funding Agency for InnovationFinnish Funding Agency for Technology & Innovation (TEKES) [1877/31/2016]; Sigrid Juselius FoundationSigrid Juselius Foundation; Finska Lakaresallskapet; Liv ochHalsa Foundation; Maire Lisko foundation
  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Savola, PaulaUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Bhattacharya, DipabarnaUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Huuhtanen, JaniUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Lonnberg, TapioUniv Turku, Finland; Abo Akad Univ, Finland (author)
  • Kankainen, MattiUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Paalanen, KirsiJyvaskyla Cent Hosp, Finland (author)
  • Tyster, MikkoUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Lepisto, MaijaUniv Helsinki, Finland (author)
  • Ellonen, PekkaUniv Helsinki, Finland (author)
  • Smolander, JohannesUniv Turku, Finland; Abo Akad Univ, Finland (author)
  • Eldfors, SamuliUniv Helsinki, Finland (author)
  • Yadav, BhagwanUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Khan, SofiaUniv Turku, Finland; Abo Akad Univ, Finland (author)
  • Koivuniemi, RiittaUniv Helsinki, Finland (author)
  • Sjöwall, ChristopherLinköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)chrsj93 (author)
  • Elo, Laura L.Univ Turku, Finland; Abo Akad Univ, Finland (author)
  • Lahdesmaki, HarriAalto Univ, Finland (author)
  • Maeda, YukaNatl Canc Ctr, Japan (author)
  • Nishikawa, HiroyashiNatl Canc Ctr, Japan (author)
  • Leirisalo-Repo, MarjattaUniv Helsinki, Finland (author)
  • Sokka-Isler, TuulikkiJyvaskyla Cent Hosp, Finland; Univ Eastern Finland, Finland (author)
  • Mustjoki, SatuUniv Helsinki, Finland; Helsinki Univ Hosp, Finland (author)
  • Univ Helsinki, Finland; Helsinki Univ Hosp, FinlandUniv Turku, Finland; Abo Akad Univ, Finland (creator_code:org_t)

Related titles

  • In:Frontiers in Immunology: FRONTIERS MEDIA SA111664-3224

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