Abstract:
BACKGROUND:Plasmablasts and plasma cells play a key role in many autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study was undertaken to evaluate the potential of targeting CD38 as a plasma cell/plasmablast depletion mechanism by daratumumab in the treatment of patients with RA and SLE. METHODS:RNA-sequencing analysis of synovial biopsies from various stages of RA disease progression, flow cytometry analysis of peripheral blood mononuclear cells (PBMC) from patients with RA or SLE and healthy donors, immunohistochemistry assessment (IHC) of synovial biopsies from patients with early RA, and ex vivo immune cell depletion assays using daratumumab (an anti-CD38 monoclonal antibody) were used to assess CD38 as a therapeutic target. RESULTS:We demonstrated that the plasma cell/plasmablast-related genes CD38, XBP1, IRF4, PRDM1, IGJ and TNFSF13B are significantly up-regulated in synovial biopsies from patients with arthralgia, undifferentiated arthritis (UA), early RA and established RA as compared to healthy controls and control patients with osteoarthritis. In addition, the highest CD38 expression was observed on plasma cells and plasmablasts compared to natural killer (NK) cells, classical dendritic cells (DCs), plasmacytoid DCs (pDCs) and T cells, in blood from healthy controls and patients with SLE and RA. Furthermore, IHC showed CD38 staining in the same region as CD3 and CD138 staining in synovial tissue biopsies from patients with early RA. Most importantly, our data show for the first time that daratumumab effectively depletes plasma cells/plasmablasts in PBMC from patients with SLE and RA in a dose-dependent manner ex vivo. CONCLUSION:These results indicate that CD38 may be a potential target for RA disease interception and daratumumab should be evaluated clinically for the treatment of both RA and SLE.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Cole S,Walsh A,Yin X,Wechalekar MD,Smith MD,Proudman SM,Veale DJ,Fearon U,Pitzalis C,Humby F,Bombardieri M,Axel A,Adams H 3rd,Chiu C,Sharp M,Alvarez J,Anderson I,Madakamutil L,Nagpal S,Guo Ydoi
10.1186/s13075-018-1578-zsubject
Has Abstractpub_date
2018-05-02 00:00:00pages
85issue
1eissn
1478-6354issn
1478-6362pii
10.1186/s13075-018-1578-zjournal_volume
20pub_type
杂志文章abstract:BACKGROUND:Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for bio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1040-z
更新日期:2016-06-16 00:00:00
abstract::Ankylosing spondylitis and axial spondyloarthropathy have characteristic age- and sex-specific onset patterns, typical entheseal lesions, and marked heritability, but the integrative mechanisms causing the pathophysiological and structural alterations remain largely undefined. Myofascial tissues are integrated in the ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4532
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Reactive oxygen species (ROS) regulate the migration and invasion of fibroblast-like synoviocytes (FLS), which are key effector cells in rheumatoid arthritis (RA) pathogenesis. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) induces ROS generation and, consequently, enhances cell migration. Desp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02204-0
更新日期:2020-05-15 00:00:00
abstract::A growing body of literature has demonstrated that the multifunctional glycoprotein osteopontin (OPN), has a role in type I interferon (IFN) production and may be involved in systemic lupus erythematosus (SLE) pathogenesis. A recent report has provided further support for this, demonstrating an association between rai...
journal_title:Arthritis research & therapy
pub_type: 评论,社论
doi:10.1186/ar4172
更新日期:2013-03-08 00:00:00
abstract:INTRODUCTION:Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4300
更新日期:2013-09-16 00:00:00
abstract:RESULTS:Anti-CarP antibodies were detected in 117 patients with RA (37.9%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were...
journal_title:Arthritis research & therapy
pub_type: 已发布勘误
doi:10.1186/s13075-016-1205-9
更新日期:2016-12-16 00:00:00
abstract:INTRODUCTION:We sought to assess vascularity in wrist tenosynovitis by using power Doppler ultrasound (PDUS) and to compare detection of intra- and peritendinous vascularity with that of contrast-enhanced grey-scale ultrasound (CEUS). METHODS:Twenty-six tendons of 24 patients (nine men, 15 women; mean age ± SD, 54.4 ±...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3185
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The Vβ12-transgenic mouse was previously generated to investigate the role of antigen-specific T cells in collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. This mouse expresses a transgenic collagen type II (CII)-specific T-cell receptor (TCR) β-chain and consequently displays an ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3108
更新日期:2010-01-01 00:00:00
abstract:INTRODUCTION:The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients. METHODS:The levels of Flt...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4403
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Rheumatoid arthritis (RA) is considered a T cell driven autoimmune disease, therefore, the ability of B cell depleting biologics, e.g., anti-CD20 antibodies, to alleviate RA is unclear. This study examined the proportions of IL-17-secreting lymphocytes in the blood of healthy subjects and RA patients and d...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3541
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:To determine whether lung involvement is related to microvascular perturbations, nailfold videocapillaroscopy (NVC) was performed in patients with systemic sclerosis (SSc). METHODS:A cross-sectional study was consecutively accomplished in 152 SSc patients. NVC, a pulmonary function test and echocardiography...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1775-9
更新日期:2018-12-19 00:00:00
abstract:BACKGROUND:Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has bee...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02404-8
更新日期:2021-01-13 00:00:00
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
pub_type: 杂志文章
doi:10.1186/s13075-020-02177-0
更新日期:2020-05-04 00:00:00
abstract:BACKGROUND:Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD:Assessm...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-019-2055-z
更新日期:2019-12-04 00:00:00
abstract:INTRODUCTION:Studies in the spontaneous ankylosis model in aging male DBA/1 mice and in patients with ankylosing spondylitis provide evidence that inflammation and new tissue formation leading to joint or spine ankylosis are likely linked but largely uncoupled processes. We previously proposed the 'entheseal stress' hy...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3772
更新日期:2012-03-12 00:00:00
abstract:INTRODUCTION:Varied definitions of disc pathology exist in the literature. Magnetic Resonance Imaging (MRI) classification systems incorporate several qualitative features including disc appearance, the distinction between the nucleus and the annulus, signal intensity and intervertebral disc height. The lack of a conti...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0820-1
更新日期:2015-10-23 00:00:00
abstract::B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They are the source of the rheumatoid factors and anticitrullinated protein antibodies, which contribute to immune complex formation and complement activation in the joints. B cells are also very efficient antigen-presenting cells, ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1010
更新日期:2003-01-01 00:00:00
abstract:INTRODUCTION:Triamcinolone acetonide (TA) is used for osteoarthritis management to reduce pain, and pre-clinical studies have shown that TA limits osteophyte formation. Osteophyte formation is known to be facilitated by synovial macrophage activation. TA injections might influence macrophage activation and subsequently...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0865-1
更新日期:2015-12-05 00:00:00
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journal_title:Arthritis research & therapy
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13075-018-1753-2
更新日期:2018-11-05 00:00:00
abstract::There has been a therapeutic revolution in rheumatology over the past 15 years, characterised by a move away from oral immuno-suppressive drugs toward parenteral targeted biological therapies. The potency and relative safety of the newer agents has facilitated a more aggressive approach to treatment, with many more pa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar2594
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Cartilage oligomeric matrix protein (COMP) is found at elevated concentrations in sera of patients with joint diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). We recently showed that COMP activates complement via the alternative pathway and that COMP-C3b complexes are present in sera of ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3694
更新日期:2012-01-20 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus is a chronic autoimmune disease characterized by an abundance of autoantibodies against nuclear antigens. Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PC...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4086
更新日期:2012-11-08 00:00:00
abstract:BACKGROUND:Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients' lives. The objective...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02168-1
更新日期:2020-04-15 00:00:00
abstract::Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerate...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2198
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Human cytomegalovirus (HCMV) infection has been implicated in the development of autoimmunity, including systemic lupus erythematosus (SLE). Previously we reported that HCMV phosphoprotein 65 (pp65) could induce early onset of autoantibody and glomerulonephritis on lupus-prone NZB/W mice. This study furthe...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3481
更新日期:2011-01-01 00:00:00
abstract:INTRODUCTION:Vagus nerve stimulation (VNS) exerts beneficial anti-inflammatory effects in various animal models of inflammation, including collagen-induced arthritis, and is implicated in representing a novel therapy for rheumatoid arthritis. However, evidence of anti-inflammatory effects of VNS in humans is very scarc...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-015-0667-5
更新日期:2015-06-07 00:00:00
abstract::Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious in...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1803
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:Interleukin-1 (IL-1) blockade is the treatment of choice of cryopyrin associated periodic syndromes (CAPS). Anti-IL-1 monoclonal antibody (canakinumab) was recently registered. However no clear data are available on the optimal schedule of administration of this drug. The aim of the present study was to an...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/ar4184
更新日期:2013-02-26 00:00:00
abstract:INTRODUCTION:Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serve...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-014-0414-3
更新日期:2014-08-20 00:00:00
abstract:INTRODUCTION:Semaphorin 3A (sema3A) and neuropilin-1 (NP-1) play a regulatory role in immune responses and have a demonstrated effect on the course of collagen induced arthritis. This study was undertaken to evaluate the role of sema3A and NP-1 in the pathogenesis of systemic lupus erythematosus (SLE) and the specific ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3881
更新日期:2012-06-14 00:00:00