Abstract：
:Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characteristized by the presence of autoantibodies against double-stranded DNA (anti-dsDNA) in sera at high levels. Bacterial infections in SLE are associated with higher morbidity and mortality. Our goal was to observe the interaction between these 2 factors in the pathogenesis of lupus. We generated transgenic mice with monoclonal anti-dsDNA to investigate the development of lupus. By challenging the mice in vitro and in vivo with Toll-like receptor 4 (TLR4) ligand lipopolysaccharides (LPS), we were able to examine the role of bacterial infection in SLE. In our study, the transgenic mice with a secreted form of anti-dsDNA were found to have higher levels of anti-nuclear antibodies, anti-dsDNA, blood urea nitrogen, and proteinuria. The splenocytes of the mice stimulated with LPS secreted more anti-dsDNA, IFN-γ, and IL-10. After injecting them with LPS in vivo, we further found higher immune complex depositions and IL-10 in the kidneys of the transgenic mice. Moreover, the LPS-injected transgenic mice had higher mortality rate. This is the first transgenic model to demonstrate that only 2 risk factors, pathogenic anti-dsDNA and TLR4 activation, induce severe SLE syndromes in normal mice through the overproduction of IL-10 and IFN-γ. These findings imply that anti-dsDNA and bacterial infections have pivotal roles in the pathogenesis of SLE; the inhibition of TLR4 may be regarded as a therapeutic target.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Lee TP,Tang SJ,Wu MF,Song YC,Yu CL,Sun KHdoi
10.1016/j.jaut.2010.07.007subject
Has Abstractpub_date
2010-12-01 00:00:00pages
358-67issue
4eissn
0896-8411issn
1095-9157pii
S0896-8411(10)00082-Xjournal_volume
35pub_type
杂志文章abstract：:The incidence of the autoimmune thyroid disease Hashimoto thyroiditis (HT) has increased in recent years, and increasing evidence supports the contribution of excess iodine intake to thyroid disease. In this study, we examined the status of autophagy and apoptosis in thyroid tissues obtained from patients with HT, and...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2016.07.008
更新日期：2016-12-01 00:00:00
abstract：:Peripheral T cells can be polarized towards type 1 or type 2 cytokine immune responses during TCR engagement. Because T cell selection by peptide plus self-MHC in the thymus requires TCR engagement, we hypothesized that type 1 cytokines may polarize developing T cells. We cultured thymi from BBDR rats in adult thymus ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/s0896-8411(02)00091-4
更新日期：2003-02-01 00:00:00
abstract：:The relationships between immunological dysfunction, loss of tolerance and hematologic malignancies have been a focus of attention in attempts to understand the appearance of a higher degree of autoimmune disease and lymphoma in children with congenital immunodeficiency. Although multiple hypotheses have been offered,...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2012.09.002
更新日期：2012-12-01 00:00:00
abstract：:Therapy with anti-CD3 antibody is effective in controlling models of autoimmune diseases and can reverse or prevent rejection of grafts. We studied the in vitro immunomodulatory effect of anti-CD3 treated human T cells. CD4(+) T cells were stimulated with plate-bound anti-CD3 and cultured for 12 days after which they ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.11.007
更新日期：2008-02-01 00:00:00
abstract：:The Ro ribonucleoprotein particle (RoRNP) is the target of a variety of specific anti-protein autoantibodies produced by patients with systemic autoimmune diseases. RoRNPs, the function of which remains elusive, appear to be rather heterogeneous in terms of their molecular composition. Among several Ro proteins, a pro...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1996.0122
更新日期：1997-04-01 00:00:00
abstract：:Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupu...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2012.12.012
更新日期：2013-03-01 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
abstract：:Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 an...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2016.05.013
更新日期：2016-11-01 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：: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：:Immunoblotting was optimized to detect autoantibodies to TSH receptors from human and porcine thyroid tissue and to determine their epitope specificity. Autoantibodies to putative TSH receptor proteins in thyroid particulate membranes were detected in approximately 35% of sera from patients with Graves' disease. Howev...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(91)90164-8
更新日期：1991-06-01 00:00:00
abstract：:Our aim was to investigate presence of tumour necrosis factor (TNF) and interleukin (IL)-10 in serum and their relation to different genotypes as well as to clinical and laboratory phenotypes in patients with polymyositis and dermatomyositis. In 65 patients with poly- or dermatomyositis the inflammatory cytokine balan...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2006.06.003
更新日期：2006-08-01 00:00:00
abstract：:Among B/W-derived IgM mAb, 12.5H was selected because of its ability to recognize, in solid phase ELISAs, IgG mAb with DNA-binding activity. mAb 12.5H bound preferentially to IgG2a mAb and did not react with B/W- or BALB/c-derived IgG2a mAb with no DNA-binding activity, suggesting V region-mediated interactions. mAb 1...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1056
更新日期：1994-12-01 00:00:00
abstract：:Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2019.06.002
更新日期：2019-09-01 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：:Interventional approaches that have been successful in delaying insulin-dependent diabetes mellitus (IDDM) using antigen-based immunotherapies include parenteral immunization. It has potential for clinical application provided that effective adjuvants suitable for human use can be found. We have previously shown that ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1996.0047
更新日期：1996-06-01 00:00:00
abstract：:Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control Ig...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(92)90149-k
更新日期：1992-06-01 00:00:00
abstract：:The serum concentrations of IgM, IgG1, IgG2b, IgG3 and IgA were determined in mice of C57BL/6 background, from weaning to one year of age, by quantitative isotype-specific, indirect double sandwich enzyme-linked immunosorbent assays (ELISAs). Only limited data could be obtained for the IgG2a isotype in the present stu...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(89)90013-9
更新日期：1989-12-01 00:00:00
abstract：:Type 1 diabetes is the result of an ongoing autoimmune response to specific proteins expressed by the insulin producing beta cells. Recently, a number of beta cell autoantigens have been identified. However, their role in mediating the diabetogenic response is not known. Here we assess the relative importance of a pan...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1067
更新日期：1994-12-01 00:00:00
abstract：:Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by an inflammatory infiltrate primarily affecting the skeletal muscle and skin. Most common and peculiar cutaneous lesions include Gottron's papules, Gottron's sign and heliotrope rash. Different DM subsets have been identified until now e...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2013.11.005
更新日期：2014-02-01 00:00:00
abstract：:The murine model of human insulin dependent diabetes mellitus (IDDM), the non-obese diabetic (NOD) mouse, develops a T cell-dependent destruction of pancreatic islets. While the target antigens are unknown, there is clearly a lack of tolerance to them. Neonatal intrathymic (i.t.) antigen injection has been successfull...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1040
更新日期：1994-10-01 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：:Anti-Jo-1 antibody is characteristic of patients suffering from autoimmune-disease myositis. Since the antigen has been identified to be a histidyl-tRNA synthetase (HisRS), it is reasonable to suppose that it localizes mainly in the cytoplasm. However, contradictory results (localization in the nucleus, cytoplasm, or ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2004.01.004
更新日期：2004-05-01 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：: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 relea...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1997.0172
更新日期：1998-02-01 00:00:00
abstract：BACKGROUND:Immune mediated diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and inflammatory bowel disease (IBD) commonly affect young and adolescent females. Anti-tumor necrosis factor (TNF)-α agents are increasingly used to treat these conditions, but their safety during pregnancy remains uncl...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.jaut.2016.11.004
更新日期：2017-01-01 00:00:00
abstract：:Malathion administration at non-cholinergical doses was shown to elevate macrophage, proliferative and humoral immune responses. This study examined the effects of malathion on autoimmunity, autoantibody formation, macrophage function and mitogenic responses in MRL-lpr mice (genetically predisposed to autoimmune disea...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1997.0145
更新日期：1997-08-01 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：:Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2016.02.011
更新日期：2016-05-01 00:00:00
abstract：OBJECTIVES:Sicca symptoms occur in around 30% of rheumatoid arthritis (RA) patients. Herein, we examined the characteristics of RA patients bearing sicca symptomatology (RA-sicca) with a special focus on the immunohistopathological features of their labial minor salivary gland (LMSG) biopsies. METHODS:Our cohort inclu...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2016.06.008
更新日期：2016-09-01 00:00:00
