Abstract:
INTRODUCTION:Soluble immune aggregates bearing intact Fc fragments are effective treatment for a variety of autoimmune disorders in mice. The better to understand the mechanisms by which Fc-bearing immune complexes suppress autoimmunity, and to develop a platform for clinical translation, we created a series of fully recombinant forms of polyvalent IgG2a Fc, termed stradomers, and tested their efficacy in a therapeutic model of collagen-induced arthritis (CIA) and preventive models of both idiopathic thrombocytopenic purpura (ITP) and graft-versus-host disease (GVHD). METHODS:Stradomers were created by engineering either the human IgG2 hinge sequence (IgG2H) or the isoleucine zipper (ILZ) onto either the carboxy or amino termini of murine IgG2a Fc. Multimerization and binding to the canonical Fc receptors and the C-type lectin SIGN-RI were evaluated by using sodium dodecylsulfate-polymerase chain reaction (SDS-PAGE) and Biacore/Octet assays. The efficacy of stradomers in alleviating CIA and preventing ITP and GVHD was compared with "gold standard" therapies, including prednisolone and intravenous immune globulin (IVIG). RESULTS:Stradomers exist as both homodimeric and highly ordered sequential multimers. Higher-order multimers demonstrate increasingly stable associations with the canonic Fcγ receptors (FcγRs), and SIGN-R1, and are more effective than Fc homodimers in treating CIA. Furthermore, stradomers confer partial protection against platelet loss in a murine model ITP, but do not prevent GVHD. CONCLUSION:These data suggest that fully human stradomers might serve as valuable tools for the treatment of selected autoimmune disorders and as reagents to study the function of Fc:FcR interactions in vivo.
journal_name
Arthritis Res Therjournal_title
Arthritis research & therapyauthors
Jain A,Olsen HS,Vyzasatya R,Burch E,Sakoda Y,Mérigeon EY,Cai L,Lu C,Tan M,Tamada K,Schulze D,Block DS,Strome SEdoi
10.1186/ar4024subject
Has Abstractpub_date
2012-08-20 00:00:00pages
R192issue
4eissn
1478-6354issn
1478-6362pii
ar4024journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Interstitial lung disease (ILD) is the principal cause of death in polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for death and serious infection in PM/DM-ILD using the multicenter database. METHODS:We retrospectively reviewed baseline demographic, clinical and laboratory find...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-017-1506-7
更新日期:2018-01-11 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:The aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE. METHODS:Gene expression levels in peripheral blood cells (PBLs)...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2972
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Final data are presented for the ORAL Sequel long-term extension (LTE) study evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg twice daily (BID) for up to 9.5 years in patients with rheumatoid arthritis (RA). METHODS:Eligible patients had previously completed a phase 1, 2, or 3 qualifying ind...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1186/s13075-019-1866-2
更新日期:2019-04-05 00:00:00
abstract:INTRODUCTION:Adjustment of infliximab dosage for individuals may be useful in improving therapeutic response in rheumatoid arthritis (RA). Herein, we aimed to determine whether measurement of infliximab serum concentration modifies the therapeutic decision and improves the control of disease activity. METHODS:RA patie...
journal_title:Arthritis research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/ar2867
更新日期:2009-01-01 00:00:00
abstract::The objective of this study was to evaluate the safety and possible efficacy of IFN-beta-1a for the treatment of patients with rheumatoid arthritis (RA). Twenty-two patients with active RA were enrolled in a phase II randomized, double-blind, placebo-controlled trial of 30 microg IFN-beta-1a by weekly self-injection f...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar1026
更新日期:2004-01-01 00:00:00
abstract:INTRODUCTION:Hyperuricemia is the greatest risk factor for gout and is caused by an overproduction and/or inefficient renal clearance of urate. The fractional renal clearance of urate (FCU, renal clearance of urate/renal clearance of creatinine) has been proposed as a tool to identify subjects who manifest inefficient ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/ar4020
更新日期:2012-08-17 00:00:00
abstract:BACKGROUND:Pepsin agglutinators, discovered over 50 years ago, have been recently referred to as anti-hinge antibodies (AHAs) because of their reaction with the IgG hinge epitope. AHAs have different reactivity for each hinge epitope generated by each protease that cleaves the hinge region at different sites. Moreover,...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02251-7
更新日期:2020-06-26 00:00:00
abstract:INTRODUCTION:There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. MET...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2708
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Immunological studies of giant cell arteritis (GCA) suggest that a triggering antigen of unknown nature could generate a specific immune response. We thus decided to detect autoantibodies directed against endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in the serum of GCA patients and to i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3388
更新日期:2011-06-28 00:00:00
abstract:BACKGROUND:The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS:Fine n...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-018-1594-z
更新日期:2018-06-08 00:00:00
abstract:BACKGROUND:BoneXpert (BX) is a newly developed medical device based on digital X-ray radiogrammetry to measure human cortical bone thickness. The aim of this study was to quantify cortical bone loss of the metacarpals in patients with psoriatic arthritis (PsA) and compare these findings with other radiological scoring ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-016-1145-4
更新日期:2016-10-25 00:00:00
abstract:INTRODUCTION:Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed withi...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-015-0575-8
更新日期:2015-03-23 00:00:00
abstract::The detection of autoantibodies in human sera is an important approach to the diagnosis and management of patients with autoimmune conditions. To meet market demands, manufacturers have developed a wide variety of easy to use and cost-effective diagnostic kits that are designed to detect a variety of human serum autoa...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar782
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD i...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,随机对照试验
doi:10.1186/s13075-016-1203-y
更新日期:2016-12-30 00:00:00
abstract:INTRODUCTION:The decreased disc height characteristic of intervertebral disc (IVD) degeneration has often been linked to low back pain, and thus regeneration strategies aimed at restoring the disc extracellular matrix and ultimately disc height have been proposed as potential treatments for IVD degeneration. One such t...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2611
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we repo...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/ar2948
更新日期:2010-01-01 00:00:00
abstract::The development of spontaneous autoimmunity in inbred strains of rodents has allowed us to investigate the molecular basis of chronic inflammatory disease in ways that would not be possible in humans. Recently, two new mouse models of autoimmune inflammatory polyarthritis have been reported that demonstrate how altera...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar1185
更新日期:2004-01-01 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:OBJECTIVE:To assess the associations between aspartate transaminase/alanine transaminase ratio (DRR) and mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). PATIENTS AND METHODS:This was a retrospective cohort study, which included 522 patients with PM/DM-ILD whose...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/s13075-020-02286-w
更新日期:2020-09-20 00:00:00
abstract::Memory T cells display phenotypic heterogeneity. Surface antigens previously regarded as exclusive markers of naive T cells, such as L-selectin (CD62L), can also be detected on some memory T cells. Moreover, a fraction of CD45RO+ (positive for the short human isoform of CD45) memory T cells reverts to the CD45RA+ (pos...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar610
更新日期:2003-01-01 00:00:00
abstract::Recent genome-wide association studies have implicated the tumor necrosis factor receptor-associated factor 3-interacting protein 2 (TRAF3IP2) gene and its product, nuclear factor-kappa-B activator 1 (Act1), in the development of psoriatic arthritis (PsA). The high level of sequence homology of the TRAF3IP2 (Act1) gen...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar4071
更新日期:2012-10-31 00:00:00
abstract:INTRODUCTION:Extracellular matrix (ECM) degradation leads to malfunction of the cartilage in osteoarthritis (OA). Inflammatory cytokine interleukin-1 beta (IL-1β) functions in ECM degradation and prevents ECM synthesis by down-regulating the key transcription factor, Sox9, and consequently inhibiting ECM gene expressio...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4114
更新日期:2012-12-10 00:00:00
abstract:INTRODUCTION:Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. ...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4065
更新日期:2012-10-18 00:00:00
abstract:INTRODUCTION:The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse. METHODS:The prooxidative, antiproliferative, and cytotoxic effects...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4351
更新日期:2013-10-28 00:00:00
abstract::Interstitial lung disease is a common manifestation of autoimmune myositis that confers significant morbidity and mortality. The vulnerability of the lung may offer insight into the etiology of this autoimmune disease. The frequency and patterns of lung injury vary based on the autoantibody. Antibodies against the ami...
journal_title:Arthritis research & therapy
pub_type: 杂志文章,评审
doi:10.1186/ar3347
更新日期:2011-07-13 00:00:00
abstract:INTRODUCTION:Disease-modifying antirheumatic drugs (DMARDs) have become the treatment standard for patients with rheumatoid arthritis (RA). Although several general-population studies document that a large population of patients diagnosed with RA do not use DMARDs, little is known about this group. We explored the char...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4459
更新日期:2014-01-29 00:00:00
abstract:INTRODUCTION:Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). One of the earliest manifestations of CVD is endothelial dysfunction (ED), which can lead to functional and morphological vascular abnormalities. Several non-invasive assessments of vascular function and morp...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar4287
更新日期:2013-01-01 00:00:00
abstract:INTRODUCTION:Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-m...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar2668
更新日期:2009-01-01 00:00:00
abstract:INTRODUCTION:There is an ever-increasing need for animal models to evaluate efficacy and safety of new therapeutics in the field of rheumatoid arthritis (RA). Particularly for the early preclinical evaluation of human-specific biologicals targeting the progressive phase of the disease, there is a need for relevant anim...
journal_title:Arthritis research & therapy
pub_type: 杂志文章
doi:10.1186/ar3172
更新日期:2010-01-01 00:00:00