Abstract:
:Increasing evidence suggests that immune complexes made of anti-nuclear antibodies bound to nucleosomes released from dead cells play an important role in the pathogenesis of lupus nephritis. However, the nature and composition of apoptotic nucleosomes still remain elusive. Since large amounts of nucleosomes are released from cells undergoing apoptosis in hybridoma cell cultures, we used hybridomas secreting anti-DNA and anti-nucleosome antibodies grown in protein-free medium to generate nucleosome/anti-DNA and /anti-nucleosome immune complexes, as well as an irrelevant antibody hybridoma to generate free, non-complexed apoptotic nucleosomes. Hybridoma supernatants were fractionated by size-exclusion gel chromatography and eluted fractions with a ratio of A260/A280 >1.2 were pooled and analysed for DNA and histone profiles by gel electrophoresis and immunoblotting. When run on a 'native' gel, 'intact' apoptotic nucleosomes, free or within anti-nucleosome immune complexes, showed a strikingly reduced size compared with 'standard' nucleosomes prepared in vitro by endonuclease digestion of cell nuclei. Nucleosomal DNA (extracted from either free or complexed apoptotic nucleosomes) appeared as a major band of 160-180 bp, and had the size of 'standard' mononucleosome DNA, suggesting degradation of the histone moiety of apoptotic nucleosomes. Histone immunoblotting revealed degradation of histones H3 and H4, which was dramatically enhanced when apoptotic nucleosomes were complexed with an anti-nucleosome antibody. Our results provide direct evidence for abnormal histone composition of apoptotic nucleosomes and suggest that the fine specificity of the complexing antibody has an influence on complexed nucleosome composition.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Cabrespines A,Laderach D,Lebossé C,Bach JF,Koutouzov Sdoi
10.1006/jaut.1997.0172subject
Has Abstractpub_date
1998-02-01 00:00:00pages
19-27issue
1eissn
0896-8411issn
1095-9157pii
S0896-8411(97)90172-4journal_volume
11pub_type
杂志文章abstract::Peptidomimetic compounds that bind to major histocompatibility complex class II molecules and are resistant to cathepsins can competitively inhibit the presentation of processed protein antigens. Therefore, compounds that bind to autoimmune disease-associated class II molecules are expected to compete with autoantigen...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.09.005
更新日期:2006-11-01 00:00:00
abstract::Systemic lupus (SLE) is characterized by a break of B cell tolerance that plays a central role in disease pathophysiology. An early checkpoint defect occurs at the transitional stage leading to the survival of autoreactive B cells and consequently the production of pathogenic autoantibodies. The main purpose of our wo...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.05.002
更新日期:2019-08-01 00:00:00
abstract::To investigate a possible dysregulation of the autoantibody network in AIDS patients, the relative activity of representative natural antibodies was measured in serum IgG and IgM. These immunoglobulins were purified from two cohorts of 20 HIV-infected patients undergoing, or not, a triple combination therapy. A cohort...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0529
更新日期:2001-08-01 00:00:00
abstract::(Beta2-glycoprotein I (beta2GPI) is a plasma protein that plays an important role in the antigenic specificity of antiphospholipid autoantibodies (aPL). These antibodies are associated with an increased risk for thrombosis and recurrent foetal loss in humans. Crystallographic analysis of beta2GPI showed that its five ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2002.0590
更新日期:2002-06-01 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::Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and have been applied to treat Th2-dominant disease. In this study, we investigated whether a plasmid with the addition of 20 copies of an immunostimulatory CpG motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in tig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.01.014
更新日期:2005-05-01 00:00:00
abstract::Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)-region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD prote...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.12.005
更新日期:2015-02-01 00:00:00
abstract::Approximately 25% of mature T cells possess two distinct cytoplasmic T cell receptor (TCR) alpha-chains, due to productive gene rearrangements of both alleles. Expression of two different alpha-chains at the cell surface is a potential risk factor for development of autoimmunity. However, it has been difficult to dete...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2001.0504
更新日期:2001-06-01 00:00:00
abstract::Several polymorphisms of the insulin gene and its flanking regions (INS region) are in linkage disequilibrium and confer susceptibility to insulin-dependent diabetes (IDDM). We have analysed INS AA and AB-BB genotypes at the 1,428 FokI site (3' of the insulin gene) in 217 patients with IDDM, 402 non-diabetic first deg...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1053
更新日期:1994-10-01 00:00:00
abstract::The development of autoimmune diseases is characterized by the breakdown of mechanism(s) that are responsible for maintaining immunological tolerance against self-structures in the periphery. Several aberrations of immune cells have been described so far. Most recently quantitative and/or qualitative defects of T cell...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2010.06.018
更新日期:2010-11-01 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::Sex hormones, including estrogens, influence the immune system in a complex manner, playing an important role in the pathophysiology of autoimmune diseases. Estrogen receptors can be found in almost all cells, including those of the adaptive and innate immune systems. Depending on the relative preponderance and stimul...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.11.002
更新日期:2012-05-01 00:00:00
abstract::There is significant unmet need in the treatment of lupus nephritis (LN) patients. In this review, we highlight the role of the TWEAK/Fn14 pathway in mediating key pathologic processes underlying LN involving both glomerular and tubular injury, and thus the potential for renal protection via blockade of this pathway. ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2012.05.003
更新日期:2012-09-01 00:00:00
abstract::The costimulatory interaction between CD28 on T cells and B7-related molecules on antigen presenting cells plays an important role in a broad range of functions of the immune system, including protective immunity, tolerance induction, allograft rejection, and the development of autoimmune diseases. Monoclonal antibodi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0258
更新日期:1999-03-01 00:00:00
abstract::Serum and Ig samples obtained from a patient with Graves' disease during exacerbation and remission were evaluated in the nu/nu bioassay. Blocking of the exacerbation serum's biological activity was demonstrated by several biological assay parameters after it was mixed with the remission serum. Since this blocking eff...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80011-3
更新日期:1990-08-01 00:00:00
abstract::Gm and Km allotypes were examined in 29 myasthenia gravis patients with a thymoma and non-receptor skeletal muscle antibodies. The frequency of the phenotype Gm1,2,3;23;5,21 was significantly higher in the patients than in 292 healthy controls (P less than 0.01). Km allotype frequencies did not differ in patients and ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(90)90148-l
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND:The aberrant recognition of self-nucleic acids by the innate immune system contributes to the pathology of several autoimmune diseases. Although microbial DNA and, in certain instances, self-DNA that is released from damaged cells are primarily recognized by Toll-like receptor 9 (TLR9), recent evidence sugge...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.06.005
更新日期:2019-12-01 00:00:00
abstract::The clinical manifestations of graft rejection or autoimmune disease represent the terminal phase in a complex sequence of inflammatory events. Although the spectrum of response to injury within each tissue is normally narrowly defined, the immune mechanisms involved may be heterogeneous, influenced by the immune stat...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90052-r
更新日期:1992-04-01 00:00:00
abstract::There are two classes of autoimmune disease, organ-specific and non-organ specific or systemic. That cells producing autoantibodies are selected by antigen is strongly suggested by the presence of mutations and high affinity antibody. T-cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic ben...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90015-i
更新日期:1992-04-01 00:00:00
abstract::Catastrophic antiphospholipid (Asherson's) syndrome (cAPS) was described in the past as a severe variant of the antiphospholipid syndrome (APS). Currently growing evidence suggests it is a unique condition. This statement is based on several clinical and physiopathological features that although not well understood de...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2008.10.003
更新日期:2009-02-01 00:00:00
abstract::Selective homing of autoreactive lymphocytes to the pancreatic islets of Langerhans is essential for triggering the cascade of molecular and cellular interactions which culminate in the specific destruction of the insulin-producing beta-cells. Based upon the sequential multistep model of lymphocyte adhesion to the end...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1069
更新日期:1994-12-01 00:00:00
abstract::Systemic lupus erythematosus is a multi-system disease characterized by wide-spread DNA methylation changes. To identify epigenetic susceptibility loci for lupus nephritis, genome-wide DNA methylation changes in naïve CD4+ T cells were compared between two sets of lupus patients with and without a history of renal inv...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2015.05.003
更新日期:2015-07-01 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::The great majority of insulin-specific T cell clones isolated from islets of NOD mice react with insulin peptide B-(9-23) (amino acids 9-23 of the insulin B chain). The T cell receptors of these clones contain diverse beta-chains but restricted alpha-chains. The dominant alpha-chain motif is a V alpha 13 segment (10 o...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0134
更新日期:1997-06-01 00:00:00
abstract::Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2018.05.009
更新日期:2018-08-01 00:00:00
abstract::Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies dependi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2011.12.001
更新日期:2012-05-01 00:00:00
abstract::Various specific and non-specific environmental factors have been associated with the induction and/or exacerbation of disease activity in patients with Crohn's disease and ulcerative colitis. One such factor is the potential role of ingested ultrafine particles. In fact, based on a Western diet, recent data suggest t...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0342
更新日期:2000-02-01 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::Autoantibodies to adrenal medulla that gave a diffuse immunofluorescent staining pattern were detected in 17 out of 107 (16%) patients with newly diagnosed Type I diabetes mellitus, in 13 out of 178 (7%) patients with long lasting disease but in none of 80 mixed control sera tested. The antibodies were of IgG class an...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(88)90028-5
更新日期:1988-06-01 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