Abstract:
:We have previously described an SLE-derived human hybridoma autoantibody, 9604, which binds to activated but not to resting platelets, inhibits platelet aggregation, and immunoprecipitates a surface-labelled poly-peptide of 32,000 molecular weight (MW) (p32). In the present study, using a murine monoclonal anti-p32 antibody (8E8), we show that p32 is responsible for the binding of 9604 to activated platelets. First, 8E8 bound to the surface of activated but not resting platelets, as detected by flow cytometry, showing saturation with 1900 antibody molecules bound/platelet and a Kd of 72 nM. Second, complete inhibition of the binding of 9604 to ADP-activated platelets by 8E8 and inhibition of the reactivity of 8E8 with p32 by 9604 demonstrated that 8E8 and 9604 recognize the same 32,000 MW platelet polypeptide. Isolation of platelet proteins, using an 8E8-affinity column, showed high MW bands corresponding to multimers of p32 under non-reducing conditions, and isolated p32 tended to self-associate even under reducing conditions. High performance liquid chromatography (HPLC) demonstrated that the native p32-containing protein has an approximate MW of 450,000. A comparison of the functional properties of murine monoclonal 8E8 and human monoclonal 9604 revealed that both antibodies are cytotoxic to platelets in 51Cr-release assays. In contrast, 8E8, unlike 9604, did not affect platelet aggregation, suggesting that different epitopes may be recognized by the two antibodies. These findings demonstrate that p32 is a subunit of an activation marker that is expressed on the surface of activated platelets and recognized by an SLE-derived anti-platelet autoantibody. Our data also indicate that murine monoclonal antibodies produced against platelet autoantigens may not mimic the functional activities of spontaneously occurring autoantibodies, probably due to the recognition of different epitopes.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Xu H,Frojmovic MM,Wong T,Rauch Jdoi
10.1006/jaut.1995.0008subject
Has Abstractpub_date
1995-02-01 00:00:00pages
97-119issue
1eissn
0896-8411issn
1095-9157pii
S0896-8411(85)70008-Xjournal_volume
8pub_type
杂志文章abstract::MIV-7 is a human monoclonal antibody that binds to DNA and carries a pathogenic anti-DNA idiotype 16/6. The antibody was generated by fusing peripheral blood lymphocytes of a healthy donor which were stimulated with an anti-idiotypic antibody to B11 (a human mAb anti-mouse mammary tumor virus-MMTV). The MIV-7, in addi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90008-e
更新日期:1992-08-01 00:00:00
abstract::The higher concordant occurrence of autoimmune diseases in monozygotic twins compared to dizygotic or sibling pairs supports the role for genetic susceptibility. For most conditions, however, concordance rates are considerably below 100% and lead to the estimate of the weight of genetics coined "heritability". In the ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2012.07.011
更新日期:2012-12-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune diseases. In both human and mouse SLE diseases, the autoimmune response targets a restricted set of autoantigens. Many of them are nucleic acids and proteins involved in the synthesis and processing of DNA or RNA, a characteristic which should ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1996.0031
更新日期:1996-04-01 00:00:00
abstract::We compared the classical immunofluorescence test (IFT) and counterimmunoelectrophoresis method (CIE) with the new immunoblotting technique (IBT) for the detection of antinuclear antibodies (ANA). Sera from 200 patients were tested in all three assays. Patients were classified as having either rheumatic disease includ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90023-6
更新日期:1988-04-01 00:00:00
abstract::TREX1 encodes a major cellular DNA exonuclease. Mutations of this gene in human cause cellular accumulation of DNA that triggers autoimmune diseases including Aicardi-Goutieres Syndrome (AGS) and systemic lupus erythematosus (SLE). We created a lupus mouse model by engineering a D18 N mutation in the Trex1 gene which ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.03.001
更新日期:2019-06-01 00:00:00
abstract::A subgroup of murine monoclonal anti-DNA antibodies bind to vascular endothelial cells either directly as a result of cross-reactivity, or indirectly through immunoglobulin-bound DNA and DNA-binding proteins on the endothelial cell membrane. To determine whether these mechanisms apply in human systemic lupus erythemat...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.9998
更新日期:1997-10-01 00:00:00
abstract::Immuno-regulatory defects, including a reduction in the number and function of regulatory T cells, play an important role in the development of autoimmune diabetes in both humans and non-obese diabetic (NOD) mice. In this study we tested the effect of introduction of FoxP3 into antigen non-specific polyclonal and anti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.02.015
更新日期:2007-06-01 00:00:00
abstract::A common epitope on S-antigen (arrestin), a potent autoantigen inducing experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor alpha (hTNF alpha) was revealed using two monoclonal antibodies to S-antigen which inhibit EAU induction. The minimal common sequence for monoclonal antibody recogniti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80048-4
更新日期:1992-02-01 00:00:00
abstract::It has been known for many years that bacteria can induce autoimmune responses in humans resulting in serious disease. Recent work has shown that a number of bacteria that colonize human mucosal surfaces exclusively express antigens on their surfaces which are molecular mimics of glycosphingolipids found on human cell...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0477
更新日期:2001-05-01 00:00:00
abstract::Cytokine expression was investigated in synovial cell cultures isolated from diseased joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Tumour necrosis factor alpha (TNF alpha) was produced spontaneously at high levels by both RA and OA synovial cells. There was no correlation between cell com...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90129-7
更新日期:1989-06-01 00:00:00
abstract::Antiphospholipid syndrome (APS) is characterized by thrombosis and pregnancy loss in the presence of antiphospholipid antibodies (aPL), mainly anticardiolipin, anti-beta2-glycoprotein I and lupus anticoagulant. However, similar to systemic lupus erythematosus, APS is also characterized by multiple other autoantibodies...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.11.011
更新日期:2008-02-01 00:00:00
abstract::A primary initiating epitope in the NOD mouse model of Type 1 Diabetes (T1D) lies between residues 9 and 23 of the insulin B chain. The B:9-23 peptide can bind to the NOD MHC class II molecule (I-Ag7) in multiple registers, but only one, (register 3, R3), creates complexes able to stimulate the majority of pathogenic ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.08.004
更新日期:2019-01-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown aetiology. Although it has been reported that T cells might be responsible for the pathogenesis of SLE, it remains unclear whether immune aberrations of SLE T cells are the primary event in this pathological process. We have recently report...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0223
更新日期:1998-10-01 00:00:00
abstract::Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(03)00083-0
更新日期:2003-08-01 00:00:00
abstract::NZB mice demonstrate common and consistent abnormalities in B-cell activation and signalling. One of the hallmark characteristics of lupus disease is the prevalent hypergammaglobulinaemia, composed primarily of anti-nuclear antibodies. In addition to the hyperproliferation seen in mice exhibiting disease, the B cells ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0607
更新日期:2002-11-01 00:00:00
abstract::It was previously shown that BALB/c mice were susceptible to experimental autoimmune encephalomyelitis induced by immunization with proteolipid protein (PLP). To determine the encephalitogenic epitopes of PLP in BALB/c mice, mice were immunized with successively smaller pools of 20-mer peptides spanning the PLP molecu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0619
更新日期:2002-12-01 00:00:00
abstract::Despite a broad clinical spectrum, paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is a family of four Hu antigens: three (Hel-N1, HuC, Hu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0337
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:To describe the clinical and laboratory features, as well as the precipitating factors, treatment and outcome of patients with catastrophic antiphospholipid syndrome (APS). METHODS:We analyzed the 280 patients included until September 2008 in the website based international registry of patients with catastro...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2009.02.008
更新日期:2009-05-01 00:00:00
abstract::Wegener's autoantigen (WA), a 29 kD multifunctional protein, is the principal target antigen of autoantibodies associated with Wegener's granulomatosis (WG). WA was first identified as proteinase 3 (PR3), which is now known to be identical with myeloblastin and AGP7. Like other lysosomal proteins, WA/PR3 displays enzy...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1993.1015
更新日期:1993-04-01 00:00:00
abstract::Immunization with antigen-specific T cells has been used successfully in the treatment of several T cell-mediated experimental autoimmune diseases, including experimental allergic encephalomyelitis, thyroiditis, and adjuvant arthritis. The aim of this study was to determine whether T-cell vaccination could be used to ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80033-2
更新日期:1990-12-01 00:00:00
abstract::The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have be...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1999.0346
更新日期:2000-02-01 00:00:00
abstract::Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been espe...
journal_title:Journal of autoimmunity
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.jaut.2011.04.002
更新日期:2011-09-01 00:00:00
abstract::Oxidative stress makes an important contribution to the development of autoimmune diabetes. We therefore tested the possible therapeutic value of two anti-oxidants, butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC), in the animal model of diabetes induced in susceptible DA rats by multiple low dose...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.01.005
更新日期:2004-06-01 00:00:00
abstract::We investigated the in vivo pathogenic potential of murine autoimmunity to peptides of the glutamate/AMPA receptor subunit 3 (GluR3). Antibodies to GluR3 are found in human epilepsy, Rasmussen's encephalitis (RE). In our accompanying paper in this issue we found that murine antibodies to the GluR3B peptide (amino acid...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0297
更新日期:1999-08-01 00:00:00
abstract::Lupus is a systemic autoimmune disease characterized by anti-nuclear antibodies in humans and genetically susceptible NZB/W mice that can cause immune complex glomerulonephritis. T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secretin...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.01.002
更新日期:2014-05-01 00:00:00
abstract::Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel str...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2018.08.009
更新日期:2018-11-01 00:00:00
abstract::HLA-DQB1 is widely considered to be the major histocompatibility complex (MHC) susceptibility gene for type 1 diabetes (T1D). However, since inheritance of the gene in T1D is recessive, the presence of the protective HLA-DQB1 0602 allele with normal nucleotide sequence in some patients raises the question of whether H...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.10.006
更新日期:2008-06-01 00:00:00
abstract::The adrenocortical response is central to recovery from experimental allergic encephalomyelitis (EAE) in the Lewis rat, as reflected by the increased severity of the disease in adrenalectomized animals. The protection conferred by glucocorticoids is related to the immunosuppressive effects of the steroid, which may in...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0020
更新日期:1996-04-01 00:00:00
abstract::The Sm antigenic complex is, besides dsDNA, the most important and specific autoimmune target in systemic lupus erythematosus (SLE). The population of anti-Sm Ab elicited is very heterogeneous in terms of epitope specificity resulting in a strong assay dependent detectability. Based on the description of a new autoant...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0545
更新日期:2001-12-01 00:00:00
abstract::In 1990 our group reported a patient with autoimmune hemolytic anemia and high titers of IgM anticardiolipin antibodies that cross-reacted with phosphatidylcholine (PTC). These autoantibodies also recognized bromelain-treated erythrocytes (BrE) and in vitro aged erythrocytes. The epitope exposed with this treatment is...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0575
更新日期:2002-03-01 00:00:00