Abstract:
:Autoimmune hepatitis (AIH) is defined as a chronic liver inflammation with loss of tolerance against hepatocytes. The etiology and pathophysiology of AIH are still poorly understood because reliable animal models are limited. Therefore, we recently introduced a model of experimental murine AIH by a self-limited adenoviral infection with the AIH type 2 antigen formiminotransferase cyclodeaminase (FTCD). We could demonstrate that break of humoral tolerance towards liver specific autoantigens like FTCD and cytochrome P450 2D6 (CYP2D6) is not dependent on the genetic background. However, the development of AIH in autoantibody positive animals is determined by genetic background genes. We could also show that the break of humoral tolerance is necessary but not sufficient for the development of AIH. In contrast the break of tolerance against the ubiquitously expressed nuclear antigens (ANAs) is strictly dependent on genetic predisposition. Priming with the UGA suppressor tRNA-associated protein (soluble liver antigen; SLA) is a strong inducer of ANA reactivity, but not sufficient to cause AIH development thereby questioning the importance of anti-SLA immune response as an important driver in AIH. Monogenetic mutations such as Aire-deficiency can cause AIH in otherwise genetically resistant strains. CONCLUSION:The results have important implications for our understanding of the pathophysiology of AIH development and for the interpretation of humoral antibody responses in AIH.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Hardtke-Wolenski M,Dywicki J,Fischer K,Hapke M,Sievers M,Schlue J,Anderson MS,Taubert R,Noyan F,Manns MP,Jaeckel Edoi
10.1016/j.jaut.2016.12.001subject
Has Abstractpub_date
2017-03-01 00:00:00pages
39-45eissn
0896-8411issn
1095-9157pii
S0896-8411(16)30364-Xjournal_volume
78pub_type
杂志文章abstract::Tight-skin (TSK) mouse, the experimental model for scleroderma, develops cutaneous hyperplasia, cardiac hypertrophy, pulmonary emphysema and autoimmunity against scleroderma target autoantigens. The cutaneous hyperplasia is associated with the accumulation of microfibrils and elastic fibers in the middle and deep derm...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0158
更新日期:1997-12-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
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更新日期:2020-07-01 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...
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更新日期:2019-08-01 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
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doi:10.1016/0896-8411(88)90028-5
更新日期:1988-06-01 00:00:00
abstract:BACKGROUND/PURPOSE:Primary Sjögren's syndrome (SS) is a chronic autoimmune disease primarily involving the exocrine glands. The clinical picture of SS ranges from exocrinopathy to systemic disease affecting the lung, kidney, liver, skin, musculockeletal and nervous systems. The morbidity of SS is mainly determined by e...
journal_title:Journal of autoimmunity
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doi:10.1016/j.jaut.2012.05.018
更新日期:2012-09-01 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::Nodding Syndrome (NS) is a fatal pediatric epilepsy of unknown etiology, accompanied by multiple neurological impairments, and associated with Onchocerca volvulus (Ov), malnutrition, war-induced trauma, and other insults. NS patients have neuroinflammation, and ~50% have cross-reactive Ov/Leiomodin-1 neurotoxic autoim...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102462
更新日期:2020-08-01 00:00:00
abstract::The effect of the immunosuppressive drug FK 506 on encephalomyelitis (EAE) in Lewis rats was studied. Treatment that began during EAE induction delayed EAE onset, but when the disease started it was chronic/progressive and of unusual severity and duration, leading to death in many animals. Treatment started after onse...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0205
更新日期:1998-08-01 00:00:00
abstract::IPEX syndrome is a congenital disorder of immune regulation caused by mutations in the FOXP3 gene, which is required for the suppressive function of naturally arising CD4 + CD25 + regulatory T cells. In this case series we evaluated serum samples from 12 patients with IPEX syndrome for the presence of common autoantib...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.06.017
更新日期:2010-11-01 00:00:00
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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
abstract:OBJECTIVE:Antiphospholipid syndrome (APS) is an acquired thrombophilia characterized by recurrent thrombosis and/or pregnancy morbidity, in the presence of antibodies to β2 glycoprotein-I (β2GPI), prothrombin or Lupus anticoagulant (LA). Anti-β2GPI antibodies recognize complexes of β2GPI dimers with CXCL4 chemokine and...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102527
更新日期:2020-12-01 00:00:00
abstract::GAD65 (glutamic acid decarboxylase) is an important autoantigen in both type 1 (insulin-dependent) diabetes mellitus (IDDM) and the neurological autoimmune disease stiff-man syndrome (SMS), and is expressed in pancreatic islets as well as the nervous system. Still, only 30% of SMS patients also have type 1 diabetes. T...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0280
更新日期:1999-06-01 00:00:00
abstract::The effector mechanisms responsible for autoimmune beta cell destruction in insulin dependent (type 1) diabetes (IDD) remain elusive. In order to investigate whether T lymphocytes bearing the gamma-delta T cell receptor (gamma delta+ T cells) could be involved in this process, we measured percentages of peripheral blo...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90055-h
更新日期:1991-12-01 00:00:00
abstract::Allogeneic hematopoietic cell transplantation (HCT) is an increasingly widely used treatment modality in hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual malignancy after alloge...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2007.12.002
更新日期:2008-05-01 00:00:00
abstract::Autoimmunity is a field that has only been around for a little over a century. Initially, it was thought that autoimmunity could not happen, that the body would never turn on itself (i.e. "horror autotoxicus"). It was only around the First World War that autoimmunity was recognized as the pathogenesis of various disea...
journal_title:Journal of autoimmunity
pub_type: 社论,历史文章
doi:10.1016/j.jaut.2013.12.019
更新日期:2014-02-01 00:00:00
abstract::The pathogenetic mechanisms of organ-specific autoimmune diseases remain obscured by the complexity of the genetic and environmental factors participating in the breakdown of tolerance. A unique opportunity to study the pathogenesis of human autoimmunity is provided by autoimmune polyendocrinopathy-candidiasis-ectoder...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.07.008
更新日期:2010-12-01 00:00:00
abstract::The role of the innate immune system has been established in the initiation and perpetuation of inflammatory disease, but less attention has been paid to its role in the resolution of inflammation and return to homeostasis. Toll-like receptor (TLR) expression profiles were analysed in tissues with differing disease st...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2021.102597
更新日期:2021-01-22 00:00:00
abstract::The development of insulin dependent diabetes mellitus (IDDM) and diabetes in the diabetes prone (DP) BB rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have been implicated but not proven to play a pathogenetic role in BB rats due to the increased NK cell number and a...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(95)80021-2
更新日期:1995-12-01 00:00:00
abstract::Previous studies have indicated that blood mononuclear cells from 15-20% of patients with systemic lupus erythematosus (SLE) carry elevated levels of hsp90, a heat shock protein associated with steroid receptors in cells. We analysed surface expression of hsp90 on mononuclear cells (lymphocytes and monocytes) from pat...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90194-u
更新日期:1992-12-01 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::Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mo...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2019.03.007
更新日期:2019-06-01 00:00:00
abstract::The complement component C4 is encoded by two genes: C4A and C4B on human chromosome 6p in the major histocompatibility complex (MHC). Most studies have linked the deficiencies in C4 with systemic lupus erythematosus (SLE) in Angio-Irish, North American, Black American, Mexican American, Australian and Japanese popula...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2005.04.004
更新日期:2005-08-01 00:00:00
abstract::The major targets of the disease-specific autoantibodies to citrullinated proteins (ACPA) in synovium of rheumatoid arthritis (RA) patients are borne by the citrullinated α- and β-chains of fibrin. We demonstrated that ACPA target a limited set of citrullinated fibrin peptides and particularly four multicitrullinated ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2011.07.003
更新日期:2011-12-01 00:00:00
abstract::The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with m...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1999.0325
更新日期:1999-11-01 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::Physiologically, HLA Class II molecules are primarily expressed on immunoregulatory cells. In recent years, it has been shown that tissues affected by autoimmunity, including beta cells of 'diabetic' pancreases, 'inappropriately' express these glycoproteins. Cytokines are potent Class II inducers on a variety of cells...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(89)90127-3
更新日期:1989-06-01 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::To investigate patterns of autoreactivity in Sjögren's syndrome, the epitope specificity of anti-La antibodies was determined using recombinant antigens bearing sequences of the amino, middle, and carboxyl portions of the La molecule. Sera from patients with primary as well as secondary Sjögren's syndrome reacted with...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90161-3
更新日期:1989-08-01 00:00:00
abstract::A dual isotype (IgG, IgA) enzyme-linked immunosorbent assay (ELISA) designed to provide enhanced detection of primary biliary cirrhosis (PBC)-specific autoantibodies against both major mitochondrial and nuclear antigens has been developed and recently become commercially available. The assay (PBC Screen) simultaneousl...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.09.005
更新日期:2010-12-01 00:00:00
abstract::The standard treatment of thrombosis related to antiphospholipid antibodies is lifelong high-intensity oral anticoagulation. This standard is primarily based on retrospective evaluations of such patients. In this paper we give a summary of current treatment of deep leg vein thrombosis, pulmonary embolism, ischaemic st...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0395
更新日期:2000-09-01 00:00:00