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 ...
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Elsevier BV,2023
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-509059
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-509059URI
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https://doi.org/10.1016/j.jaut.2023.103022DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:153336655URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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)
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Sahlstrom, PeterKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Thyagarajan, RadhaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Boada, Juan Sebastian DiazKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Hansson, MonikaKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Mathsson Alm, LindaUppsala universitet,Institutionen för immunologi, genetik och patologi,Thermo Fisher Sci, Uppsala, Sweden.(Swepub:uu)limat990
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Gerstner, ChristinaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Sippl, NatalieKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Israelsson, LenaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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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.
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Steen, JohannaKarolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Klareskog, LarsKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Rethi, BenceKarolinska Institutet
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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)
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Diaz-Gallo, Lina -MarcelaKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Malmstrom, VivianneKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Gronwall, CarolineKarolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
(author)
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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.
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In:Journal of Autoimmunity: Elsevier BV1360896-84111095-9157
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Hensvold, Aase
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Horuluoglu, Begu ...
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Sahlstrom, Peter
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Thyagarajan, Rad ...
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Boada, Juan Seba ...
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Hansson, Monika
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Mathsson Alm, Li ...
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Gerstner, Christ ...
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Sippl, Natalie
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Israelsson, Lena
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Wedin, Rikard
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Steen, Johanna
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Klareskog, Lars
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Rethi, Bence
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Catrina, Anca I.
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Diaz-Gallo, Lina ...
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Malmstrom, Vivia ...
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Gronwall, Caroli ...
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