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. The specific pathological mechanisms of TWEAK - namely promoting inflammation, renal cell proliferation and apoptosis, vascular activation and fibrosis - are described, with supporting data from animal models and in vitro systems. Furthermore, we detail the translational relevance of these mechanisms to clinical readouts in human LN. We present the opportunity for an anti-TWEAK therapeutic as a renal protective agent to improve efficacy relative to current standard of care treatments hopefully without increased safety risk, and highlight a phase II trial with BIIB023, an anti-TWEAK neutralizing antibody, designed to assess efficacy in LN patients. Taken together, targeting the TWEAK/Fn14 axis represents a potential new therapeutic paradigm for achieving renal protection in LN patients.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Michaelson JS,Wisniacki N,Burkly LC,Putterman Cdoi
10.1016/j.jaut.2012.05.003subject
Has Abstractpub_date
2012-09-01 00:00:00pages
130-42issue
3eissn
0896-8411issn
1095-9157pii
S0896-8411(12)00060-1journal_volume
39pub_type
杂志文章,评审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：:Epigenetic changes are of crucial importance in the etiopathogenesis of autoimmune liver diseases. Among these, there is limited agreement on the definitions and treatment of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndromes, we evaluated a large series of consecutive patients with PBC (...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2012.10.004
更新日期：2013-03-01 00:00:00
abstract：:Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation wit...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2011.05.007
更新日期：2011-09-01 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：: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：:Polymyositis is classified as a separate entity among idiopathic inflammatory myopathies but it is considered as the least common since it is an exclusion diagnosis. This myopathy usually presents with subacute-chronic symmetric proximal limb weakness, although some extramuscular manifestations are common. Creatine ki...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2014.01.025
更新日期：2014-02-01 00:00:00
abstract：:In a proliferation assay, peripheral blood lymphocytes (PBL) from a relatively small proportion of myasthenia gravis (MG) patients and from controls responded to Torpedo acetylcholine receptor (T-AChR), which shows approximately 75% homology with the human AChR. Over 50% of MG patients responded to recombinant human A...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(89)90121-2
更新日期：1989-06-01 00:00:00
abstract：:Multiple sclerosis (MS), an inflammatory and demyelinating autoimmune disease of CNS has both, a genetic and an environmental predisposition. Among all the genetic factors associated with MS susceptibility, HLA class II haplotypes such as DR2/DQ6, DR3/DQ2, and DR4/DQ8 show the strongest association. Although a direct ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2011.05.001
更新日期：2011-09-01 00:00:00
abstract：OBJECTIVE:To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis. METHODS:Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compare...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2020.102481
更新日期：2020-09-01 00:00:00
abstract：:In some circumstances cyclosporine (CyA) induces autoimmune phenomena, and a lethal form of syngeneic graft-vs-host disease (SGVHD) can be induced in rats by the administration of CyA. Although several rat strains develop this disease, in this study, we report that of six mouse strains tested, only the DBA/2 strain de...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(91)90030-g
更新日期：1991-04-01 00:00:00
abstract：:TNF-alpha is a pleiotropic cytokine that is constitutively expressed in the thymus. This cytokine has opposing effects on type 1 diabetes mellitus (T1DM) as non-obese diabetic (NOD) mice administered TNF-alpha early in life experience an acceleration in disease onset while TNF-alpha administered to adult NOD mice are ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2007.06.002
更新日期：2007-09-01 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：: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：:Promiscuous expression of a plethora of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential for central tolerance. This promiscuous gene expression (pGE) is characterized by inclusion of a broad range of TRAs and by its mosaic expression patterns, i.e. each antigen is only expre...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2015.10.001
更新日期：2016-02-01 00:00:00
abstract：:Our purpose was to evaluate the role of Epstein-Barr virus (EBV) in the production of antiperinuclear factor (APF), a rheumatoid arthritis (RA)-specific marker, and the autoimmunogenicity of 'perinuclear antigens' (PNA) found within the buccal mucosa epithelial cells used as a substrate in the APF assay. Fifty APF-pos...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1994.1035
更新日期：1994-08-01 00:00:00
abstract：:Sjögren's syndrome (SS) is an autoimmune disease with a predisposition to transform into a B-cell lymphoma. Stable B-cell lines were established (without exogenous stimulation other than fetal bovine serum) from the peripheral blood of three SS patients. These cell lines secreted immunoglobulin (either IgG, IgM or bot...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(89)90172-8
更新日期：1989-08-01 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：:Costimulatory molecules are cell-surface glycoproteins that can direct, modulate and fine tune immune responses. B7-2(CD86) costimulatory molecules are considered as major regulators of T cell responses, acting by appropriate interactions with the stimulatory CD28 or inhibitory CTLA-4 receptors found on T cells. Altho...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2010.06.006
更新日期：2010-11-01 00:00:00
abstract：:Interleukin-2 (IL-2) gene regulation was investigated in primary cultures of highly purified human peripheral blood CD28+ T cells. Two discrete mechanisms for induction of T-cell proliferation could be distinguished by examining cell cycle progression and the expression of the IL-2 gene. Stimulation of cells by CD3 Mo...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/0896-8411(89)90117-0
更新日期：1989-06-01 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：:Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires life-long immunosuppression. Frequent relapses after discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current therapies. As steroid therapy preferentially depletes intrahepatic regula...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2020.102591
更新日期：2021-02-01 00:00:00
abstract：:University of California at Davis (UCD) lines 200 and 206 chickens develop a hereditary systemic scleroderma-like connective tissue disease characterized by severe lymphocytic infiltration and excessive accumulation of collagen in skin and internal organs. The immune system seems to play an important role in the devel...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1995.0057
更新日期：1995-10-01 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：: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：:Autoantigen-specific TCR transgenic mice allow us to assess the role of T cells in autoimmunity. We have recently generated humanized TAZ10 transgenic mice expressing the human TCR specific for the immunodominant epitope of thyroid peroxidase (TPO). We have shown that these transgenic mice do not undergo tolerance in ...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1016/j.jaut.2005.01.003
更新日期：2005-03-01 00:00:00
abstract：:The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunolog...
journal_title：Journal of autoimmunity
pub_type： 杂志文章
doi：10.1006/jaut.1996.0100
更新日期：1996-12-01 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：:CD4(+) IFN-gamma-producing Th1 cells have long been associated with the pathogenesis of many organ-specific autoimmune diseases; however, the observation of disease in mice deficient in molecules involved in Th1 cell differentiation raised the possibility that other effector T cells were responsible for inducing autoi...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/j.jaut.2008.04.017
更新日期：2008-11-01 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：:Many years of work, multiplex family collection and endless genotyping finally give fruit. The original aim cannot be lost. The aim is not only to identify mutations involved in susceptibility for systemic lupus erythematosus (SLE) but to elucidate the disease pathogenesis as well. After genetics comes the biology. We...
journal_title：Journal of autoimmunity
pub_type： 杂志文章,评审
doi：10.1016/s0896-8411(03)00093-3
更新日期：2003-09-01 00:00:00
