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Search: onr:"swepub:oai:DiVA.org:uu-509059" > The human bone marr...

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  • Hensvold, AaseKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.;Stockholm Hlth Reg, Acad Specialist Ctr, Ctr Rheumatol, Stockholm, Sweden. (author)

The human bone marrow plasma cell compartment in rheumatoid arthritis-Clonal relationships and anti-citrulline autoantibody producing cells

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier BV,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-509059
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-509059URI
  • https://doi.org/10.1016/j.jaut.2023.103022DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:153336655URI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • A majority of circulating IgG is produced by plasma cells residing in the bone marrow (BM). Long-lived BM plasma cells constitute our humoral immune memory and are essential for infection-specific immunity. They may also provide a reservoir of potentially pathogenic autoantibodies, including rheumatoid arthritis (RA)-associated anti-citrullinated protein autoantibodies (ACPA). Here we investigated paired human BM plasma cell and peripheral blood (PB) B-cell repertoires in seropositive RA, four ACPA+ RA patients and one ACPA- using two different single-cell approaches, flow cytometry sorting, and transcriptomics, followed by recombinant antibody generation. Immunoglobulin (Ig) analysis of >900 paired heavy-light chains from BM plasma cells identified by either surface CD138 expression or transcriptome profiles (including gene expression of MZB1, JCHAIN and XBP1) demonstrated differences in IgG/A repertoires and N-linked glycosylation between patients. For three patients, we identified clonotypes shared between BM plasma cells and PB memory B cells. Notably, four individuals displayed plasma cells with identical heavy chains but different light chains, which may indicate receptor revision or clonal convergence. ACPA-producing BM plasma cells were identified in two ACPA+ patients. Three of 44 recombinantly expressed monoclonal antibodies from ACPA+ RA BM plasma cells were CCP2+, specifically binding to citrullinated peptides. Out of these, two clones reacted with citrullinated histone-4 and activated neutrophils. In conclusion, single-cell investigation of B-cell repertoires in RA bone marrow provided new understanding of human plasma cells clonal relationships and demonstrated pathogenically relevant disease-associated autoantibody expression in long-lived plasma cells.

Subject headings and genre

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  • Horuluoglu, BegumKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Sahlstrom, PeterKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Thyagarajan, RadhaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Boada, Juan Sebastian DiazKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Hansson, MonikaKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Mathsson Alm, LindaUppsala universitet,Institutionen för immunologi, genetik och patologi,Thermo Fisher Sci, Uppsala, Sweden.(Swepub:uu)limat990 (author)
  • Gerstner, ChristinaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Sippl, NatalieKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Israelsson, LenaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Wedin, RikardKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Dept Trauma & Reparat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. (author)
  • Steen, JohannaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Klareskog, LarsKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Rethi, BenceKarolinska Institutet (author)
  • Catrina, Anca I.Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.;Stockholm Hlth Reg, Acad Specialist Ctr, Ctr Rheumatol, Stockholm, Sweden. (author)
  • Diaz-Gallo, Lina -MarcelaKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Malmstrom, VivianneKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Gronwall, CarolineKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden. (author)
  • Karolinska InstitutetKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.;Stockholm Hlth Reg, Acad Specialist Ctr, Ctr Rheumatol, Stockholm, Sweden. (creator_code:org_t)

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  • In:Journal of Autoimmunity: Elsevier BV1360896-84111095-9157

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