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  • Wang, YanKarolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden (author)

Rheumatoid arthritis patients display B-cell dysregulation already in the naive repertoire consistent with defects in B-cell tolerance

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-12-27
  • Nature Publishing Group,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-163473
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-163473URI
  • https://doi.org/10.1038/s41598-019-56279-0DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-406182URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142857931URI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Funding Agencies|UCB PharmaUCB Pharma SA; Swedish Research CouncilSwedish Research Council; Swedish Rheumatism Association, King Gustaf Vs 80-year Foundation; Ake Wibergs stiftelse; FOREUM, Foundation for Research in Rheumatology; European Research Council (ERC) under the European UnionEuropean Research Council (ERC); EU/EFPIA Innovative Medicines Initiative (IMI) [BTCure 115142, RTCure 777357]; Karolinska InstituteKarolinska Institutet
  • B cells are postulated to be central in seropositive rheumatoid arthritis (RA). Here, we use exploratory mass cytometry (n = 23) and next-generation sequencing (n = 19) to study B-cell repertoire shifts in RA patients. Expression of several B-cell markers were significantly different in ACPA(+) RA compared to healthy controls, including an increase in HLA-DR across subsets, CD22 in clusters of IgM(+) B cells and CD11c in IgA(+) memory. Moreover, both IgA(+) and IgG(+) double negative (IgD(-) CD27(-)) CD11c(+) B cells were increased in ACPA+ RA, and there was a trend for elevation in a CXCR5/CCR6(high) transitional B-cell cluster. In the RA BCR repertoire, there were significant differences in subclass distribution and, notably, the frequency of VH with low somatic hypermutation (SHM) was strikingly higher, especially in IgG1 (p amp;lt; 0.0001). Furthermore, both ACPA(+) and ACPA(-) RA patients had significantly higher total serum IgA and IgM compared to controls, based on serology of larger cohorts (n = 3494 IgA; n = 397 IgM). The observed elevated Ig-levels, distortion in IgM(+) B cells, increase in double negative B cells, change in B-cell markers, and elevation of unmutated IgG(+) B cells suggests defects in B-cell tolerance in RA. This may represent an underlying cause of increased polyreactivity and autoimmunity in RA.

Subject headings and genre

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

  • Lloyd, Katy A.Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden (author)
  • Melas, IoannisUCB Pharma, Slough, Berks, England (author)
  • Zhou, DianaKarolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden (author)
  • Thyagarajan, RadhaKarolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden (author)
  • Lindqvist, JoakimKarolinska Institutet (author)
  • Hansson, MonikaKarolinska Institutet (author)
  • Svärd, Anna,1964-Uppsala universitet,Linköpings universitet,Medicinska fakulteten,Avdelningen för neuro- och inflammationsvetenskap,Uppsala Univ, Sweden,Centrum för klinisk forskning Dalarna,Linkoping Univ, Dept Clin & Expt Med, Div Rheumatol, Linkoping, Sweden(Swepub:uu)annsv349 (author)
  • Mathsson-Alm, LindaUppsala universitet,Klinisk immunologi,Thermo Fisher Sci, Sweden; Uppsala Univ, Sweden(Swepub:uu)limat990 (author)
  • Kastbom, AlfLinköpings universitet,Medicinska fakulteten,Avdelningen för neuro- och inflammationsvetenskap,Region Östergötland, Reumatologiska kliniken i Östergötland,Linkoping Univ, Dept Clin & Expt Med, Div Rheumatol, Linkoping, Sweden(Swepub:liu)alfka05 (author)
  • Lundberg, KarinKarolinska Institutet (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • Catrina, Anca I.Karolinska Institutet (author)
  • Rapecki, StephenUCB Pharma, Slough, Berks, England (author)
  • Malmstrom, VivianneKarolinska Institutet (author)
  • Gronwall, CarolineKarolinska Institutet (author)
  • Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, SwedenUCB Pharma, Slough, Berks, England (creator_code:org_t)

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  • In:Scientific Reports: Nature Publishing Group92045-2322

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