Circulating autoreactive proteinase 3<SUP>+</SUP> B cells and tolerance checkpoints in ANCA-associated vasculitis
DC Field | Value | Language |
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dc.contributor.author | Berti, Alvise | - |
dc.contributor.author | Hillion, Sophie | - |
dc.contributor.author | Hummel, Amber M. | - |
dc.contributor.author | Son, Young Min | - |
dc.contributor.author | Chriti, Nedra | - |
dc.contributor.author | Peikert, Tobias | - |
dc.contributor.author | Carmona, Eva M. | - |
dc.contributor.author | Abdulahad, Wayel H. | - |
dc.contributor.author | Heeringa, Peter | - |
dc.contributor.author | Harris, Kristina M. | - |
dc.contributor.author | St Clair, E. William | - |
dc.contributor.author | Brunetta, Paul | - |
dc.contributor.author | Fervenza, Fernando C. | - |
dc.contributor.author | Langford, Carol A. | - |
dc.contributor.author | Kallenberg, Cees G. M. | - |
dc.contributor.author | Merkel, Peter A. | - |
dc.contributor.author | Monach, Paul A. | - |
dc.contributor.author | Seo, Philip | - |
dc.contributor.author | Spiera, Robert F. | - |
dc.contributor.author | Stone, John H. | - |
dc.contributor.author | Grandi, Guido | - |
dc.contributor.author | Sun, Jie | - |
dc.contributor.author | Pers, Jacques-Olivier | - |
dc.contributor.author | Specks, Ulrich | - |
dc.contributor.author | Cornec, Divi | - |
dc.date.accessioned | 2024-02-19T00:30:57Z | - |
dc.date.available | 2024-02-19T00:30:57Z | - |
dc.date.issued | 2021-11 | - |
dc.identifier.issn | 2324-7703 | - |
dc.identifier.issn | 2379-3708 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/72077 | - |
dc.description.abstract | BACKGROUND. Little is known about the autoreactive B cells in antineutrophil cytoplasmic antibody-associated (ANCA-associated) vasculitis (AAV). We aimed to investigate tolerance checkpoints of circulating antigen-specific proteinase 3-reactive (PR3(+)) B cells. METHODS. Multicolor flow cytometry in combination with bioinformatics and functional in vitro studies were performed on baseline samples of PBMCs from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-AAV and myeloperoxidase-AAV (MPO-AAV) and 27 healthy controls (HCs). Clinical data and outcomes from the trial were correlated with PR3(+) B cells (total and subsets). RESULTS. The frequency of PR3(+) B cells among circulating B cells was higher in participants with PR3AAV (4.77% median [IQR, 3.98%-6.01%]) than in participants with MPO-AAV (3.16% median [IQR, 2.51%-5.22%]) and participants with AAV compared with HCs (1.67% median [IQR,1.27%-2.16%], P< 0.001 for all comparisons), implying a defective central tolerance checkpoint in patients with AAV. Only PBMCs from participants with PR3-AAV contained PR3(+) B cells capable of secreting PR3-ANCA IgG in vitro, proving they were functionally distinct from those of participants with MPO-AAV and HCs. Unsupervised clustering identified subtle subsets of atypical autoreactive PR3(+) memory B cells accumulating through the maturation process in patients with PR3-AAV. PR3(+) B cells were enriched in the memory B cell compartment of participants with PR3-AAV and were associated with higher serum CXCL13 levels. suggesting an increased germinal center activity. PR3(+) B cells correlated with systemic inflammation (C-reactive protein and erythrocyte sedimentation rate. P < 0.05) and complete remission (P< 0.001). CONCLUSION. This study suggests the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients with PR3-AAV, elucidating the selection process of autoreactive B cells. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | AMER SOC CLINICAL INVESTIGATION INC | - |
dc.title | Circulating autoreactive proteinase 3<SUP>+</SUP> B cells and tolerance checkpoints in ANCA-associated vasculitis | - |
dc.type | Article | - |
dc.identifier.doi | 10.1172/jci.insight.150999 | - |
dc.identifier.bibliographicCitation | JCI INSIGHT, v.6, no.22 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.wosid | 000721572100001 | - |
dc.identifier.scopusid | 2-s2.0-85120363030 | - |
dc.citation.number | 22 | - |
dc.citation.title | JCI INSIGHT | - |
dc.citation.volume | 6 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordPlus | WEGENERS-GRANULOMATOSIS | - |
dc.subject.keywordPlus | AUTOANTIBODIES | - |
dc.subject.keywordPlus | PR3 | - |
dc.subject.keywordPlus | MYELOPEROXIDASE | - |
dc.subject.keywordPlus | RECOGNITION | - |
dc.subject.keywordPlus | SPECIFICITY | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | BIOMARKERS | - |
dc.subject.keywordPlus | ANTIBODIES | - |
dc.subject.keywordPlus | RITUXIMAB | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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