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The human bone marr...
The human bone marrow plasma cell compartment in rheumatoid arthritis-Clonal relationships and anti-citrulline autoantibody producing cells
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- Hensvold, Aase (author)
- Karolinska 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.
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- Horuluoglu, Begum (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Sahlstrom, Peter (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Thyagarajan, Radha (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Boada, Juan Sebastian Diaz (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Hansson, Monika (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Mathsson Alm, Linda (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Thermo Fisher Sci, Uppsala, Sweden.
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- Gerstner, Christina (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Sippl, Natalie (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Israelsson, Lena (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Wedin, Rikard (author)
- Karolinska 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, Johanna (author)
- Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Klareskog, Lars (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Rethi, Bence (author)
- Karolinska Institutet
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- Catrina, Anca I. (author)
- Karolinska 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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- Diaz-Gallo, Lina -Marcela (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Malmstrom, Vivianne (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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- Gronwall, Caroline (author)
- Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.
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Karolinska 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. (creator_code:org_t)
- Elsevier BV, 2023
- 2023
- English.
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In: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 136
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Abstract
Subject headings
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- 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)
Keyword
- Bone marrow
- Plasma cells
- Rheumatoid arthritis
- Antibody repertoires
- Anti-Citrullinated protein autoantibodies 
- (ACPA)
- Anti-CCP
- Receptor revision
- Clonal convergence
- Ig repertoire
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Journal of Autoi ...
- By the university
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Uppsala University
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Karolinska Institutet