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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006964naa a2200685 4500
001oai:DiVA.org:uu-509059
003SwePub
008230816s2023 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:153336655
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5090592 URI
0247 a https://doi.org/10.1016/j.jaut.2023.1030222 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1533366552 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Hensvold, Aaseu 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.4 aut
2451 0a The human bone marrow plasma cell compartment in rheumatoid arthritis-Clonal relationships and anti-citrulline autoantibody producing cells
264 1b Elsevier BV,c 2023
338 a electronic2 rdacarrier
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reumatologi och inflammation0 (SwePub)302102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Rheumatology and Autoimmunity0 (SwePub)302102 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng
653 a Bone marrow
653 a Plasma cells
653 a Rheumatoid arthritis
653 a Antibody repertoires
653 a Anti-Citrullinated protein autoantibodies&nbsp
653 a (ACPA)
653 a Anti-CCP
653 a Receptor revision
653 a Clonal convergence
653 a Ig repertoire
7001 a Horuluoglu, Begumu Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Sahlstrom, Peteru Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Thyagarajan, Radhau Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Boada, Juan Sebastian Diazu Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Hansson, Monikau Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Mathsson Alm, Lindau Uppsala universitet,Institutionen för immunologi, genetik och patologi,Thermo Fisher Sci, Uppsala, Sweden.4 aut0 (Swepub:uu)limat990
7001 a Gerstner, Christinau Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Sippl, Natalieu Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Israelsson, Lenau Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Wedin, Rikardu Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Dept Trauma & Reparat Med, Stockholm, Sweden.;Karolinska Univ Hosp, Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.4 aut
7001 a Steen, Johannau Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Klareskog, Larsu Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Rethi, Benceu Karolinska Institutet4 aut
7001 a Catrina, Anca I.u Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.;Stockholm Hlth Reg, Acad Specialist Ctr, Ctr Rheumatol, Stockholm, Sweden.4 aut
7001 a Diaz-Gallo, Lina -Marcelau Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Malmstrom, Vivianneu Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7001 a Gronwall, Carolineu Karolinska Institutet,Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.4 aut
7102 a Karolinska Institutetb Karolinska Univ Hosp, Karolinska Inst, Div Rheumatol, Dept Med,Ctr Mol Med, Stockholm, Sweden.;Stockholm Hlth Reg, Acad Specialist Ctr, Ctr Rheumatol, Stockholm, Sweden.4 org
7730 t Journal of Autoimmunityd : Elsevier BVg 136q 136x 0896-8411x 1095-9157
8564 u https://doi.org/10.1016/j.jaut.2023.103022y Fulltext
8564 u https://uu.diva-portal.org/smash/get/diva2:1788447/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-509059
8564 8u https://doi.org/10.1016/j.jaut.2023.103022
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:153336655

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