Abstract:
BACKGROUND:Anti-Jo-1 autoantibodies which recognize histidyl-tRNA synthetase identify patients with the rare rheumatologic disease, anti-histidyl-tRNA synthetase syndrome (Jo-1 ARS), a phenotypically distinct subset of idiopathic inflammatory myopathies (IIM). Jo-1-binding B cells (JBCs) are implicated in disease pathogenesis, yet they have not been studied directly. We therefore aimed to characterize JBCs to better understand how they expand and function in Jo-1 ARS. METHODS:We enrolled 10 IIM patients diagnosed with Jo-1 ARS, 4 patients with non-Jo-1 IIM, and 8 age- and sex-matched healthy controls. We phenotypically characterized peripheral blood mononuclear cells (PBMCs) ex vivo using flow cytometry to define the B cell subsets in which JBCs reside. We further tested their ability to differentiate into antibody-secreting cells following stimulation in vitro. RESULTS:The majority of JBCs were IgM+ (not class-switched). Compared to non-JBCs in the same donors, JBCs contained a higher percentage of autoimmune-prone CD21lo cells and were increased in the CD21lo IgM+ IgD- CD27+ memory subset relative to healthy donor B cells. Whereas non-JBCs were present in the anergic BND B cell subset, JBCs were nearly absent from this compartment. JBCs were detected among plasmablasts in some donors, but a reduced frequency of JBCs differentiated into CD38hi24- plasmablasts compared to non-JBCs present in the same wells following in vitro stimulation. CONCLUSIONS:JBCs are enriched for autoimmune-prone CD21lo B cells, some of which exhibit a memory phenotype in the peripheral repertoire of Jo-1 ARS patients. JBCs undergo limited class switch and show reduced capacity to differentiate into antibody-secreting cells. This suggests complex B cell biology exists beyond class-switched cells that differentiate to secrete anti-Jo-1 autoantibody (i.e., what is captured through serum autoantibody studies). New Jo-1 ARS therapies should thus ideally target non-class-switched JBCs in addition to those that have undergone IgG class-switching to most effectively block cross-talk with autoreactive T cells.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Young-Glazer J,Cisneros A 3rd,Wilfong EM,Smith SA,Crofford LJ,Bonami RHdoi
10.1186/s13075-020-02412-8subject
Has Abstractpub_date
2021-01-19 00:00:00pages
33issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-020-02412-8journal_volume
23pub_type
杂志文章abstract:INTRODUCTION:Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using human cell lines or monocytes of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3898
更新日期:2012-07-04 00:00:00
abstract:INTRODUCTION:The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody® with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum a...
journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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doi:10.1186/s13075-015-0532-6
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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abstract:BACKGROUND:Elevated B lymphocyte stimulator (BLyS) levels in patients with systemic lupus erythematosus (SLE) correlate positively with disease activity; BLyS expression is directly linked to interferon (IFN) pathway activation. This post hoc meta-analysis of BLISS-52 and BLISS-76 explored the relationship between base...
journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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更新日期:2010-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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journal_title:Arthritis research & therapy
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更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthr...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
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abstract::Post-traumatic osteoarthritis (PTOA) develops after joint injury. Specifically, patients with anterior cruciate ligament (ACL) injury have a high risk of developing PTOA. In this review, we outline the incidence of ACL injury that progresses to PTOA, analyze the role of ACL reconstruction in preventing PTOA, suggest p...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13075-020-02156-5
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2006-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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abstract:INTRODUCTION:Although the prevalence of arthritis dramatically increases with age, the great majority of preclinical studies concerning the mechanisms that drive arthritic joint pain have been performed in young animals. One mechanism hypothesized to contribute to arthritic pain is ectopic nerve sprouting; however, neu...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2012-05-01 00:00:00
abstract::Antibodies to double-stranded DNA are important in the pathogenesis of nephritis, a major clinical manifestation in lupus patients. Since earlier diagnosis of renal involvement may lead to better outcomes, identification of the nephritogenic specificity of lupus-associated autoantibodies is important in understanding ...
journal_title:Arthritis research & therapy
pub_type: 社论
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更新日期:2009-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2013-10-26 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2008-01-01 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2020-03-17 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章
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更新日期:2016-10-22 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
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