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 autoantigens for presentation and thereby interrupt the disease process. The first generation of such competitors developed for rheumatoid arthritis-associated HLA-DR molecules, although resistant to cathepsins, has remained sensitive to plasma proteases, and was thus unlikely to be effective in vivo. We have therefore produced a second generation of compounds that are resistant to cathepsins and stable in plasma while maintaining binding affinity for HLA-DR molecules associated with rheumatoid arthritis and multiple sclerosis. Selected compounds of this series are shown to inhibit antigen presentation in vivo, as well as effectively treat collagen induced arthritis and experimental autoimmune encephalomyelitis in HLA-DR transgenic mouse models.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Rosloniec EF,Brandstetter T,Leyer S,Schwaiger FW,Nagy ZAdoi
10.1016/j.jaut.2006.09.005subject
Has Abstractpub_date
2006-11-01 00:00:00pages
182-95issue
3eissn
0896-8411issn
1095-9157pii
S0896-8411(06)00080-1journal_volume
27pub_type
杂志文章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::A recent report identified two islet cell cytoplasmic antibody subclasses using an immunohistochemical method. The islet cell cytoplasmic antibody subclass which reacts with only Beta-cells was termed 'Beta-cell islet cell cytoplasmic antibodies' and another islet cell cytoplasmic antibody subclass which reacts with B...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1994.1028
更新日期:1994-06-01 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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1995.0008
更新日期:1995-02-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1993.1040
更新日期:1993-08-01 00:00:00
abstract::This paper describes some of the methodological problems related to the measurement of cyclosporin. The clinical value of the measurements following organ transplantation are discussed and those areas also applying to autoimmune indications are highlighted. It is concluded that the routine use of cyclosporin monitorin...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/0896-8411(92)90032-l
更新日期:1992-04-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102360
更新日期:2020-02-01 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::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
doi:10.1006/jaut.2000.0418
更新日期:2000-09-01 00:00:00
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journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2015.07.006
更新日期:2015-09-01 00:00:00
abstract::Beta(2)-glycoprotein I (beta(2)GPI) is known as a major autoantigen for antiphospholipid antibodies. Our recent data show that binding of beta(2)GPI to oxidized low-density lipoprotein (oxLDL) or to liposomes containing anionic phospholipid(s) may facilitate the presentation of beta(2)GPI's epitope by macrophages/dend...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2007.07.003
更新日期:2007-09-01 00:00:00
abstract::The BB rat spontaneously develops an insulin-dependent diabetes mellitus (IDDM) that closely resembles this disease in man. The pathogenesis involves autoimmune destruction of pancreatic islet beta-cells. In the present study, a single intraperitoneal injection of complete Freund's adjuvant (CFA) in diabetes-prone (DP...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80034-4
更新日期:1990-12-01 00:00:00
abstract::HLA-DR0401, 0403 and 0405 are associated with variable T1D susceptibilities when linked with a common HLA-DQ8 (DQA1∗0301/DQB1∗0302). It is unknown how the modest differences within the peptide binding regions of DR4 subtypes lead to distinct autoimmune risks. Since all Class II HLA molecules share the same intracellul...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.12.004
更新日期:2011-03-01 00:00:00
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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
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journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.2000.0394
更新日期:2000-09-01 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::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::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 specific contributions of islet cell microenvironment during the development of autoimmune type 1 diabetes remain unclear. The aims of this study were to identify early immune-driven abnormalities in islets and pancreatic lymph nodes of NOD mice by cDNA arrays. We compared gene expression profiles of purified isle...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.03.007
更新日期:2004-08-01 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::T cell clones reactive to beta-cell antigens prepared from different species were established in order to identify putative pathogenic T cells in human IDDM. We were able to generate T cell clones from patients, but not from controls, reactive specifically to the insulin secretory enriched fraction (ISG) of a rat insu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1995.0017
更新日期:1995-04-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contri...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2014.08.003
更新日期:2015-01-01 00:00:00
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 adenov...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2016.12.001
更新日期:2017-03-01 00:00:00
abstract::Autoimmune thyroid diseases (AITDs), i.e., Graves' disease (GD) and Hashimoto thyroiditis (HT), are the most prevalent organ-specific autoimmune diseases, but their pathogenesis is still incompletely understood. The PD-1/PD-L1 pathway is an important mechanism of peripheral tolerance that has not been investigated in ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.05.013
更新日期:2019-09-01 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::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::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::IgA-, IgM- and IgG-containing immune complexes (CIC) were detected in 48, 19 and 12% of 52 patients with primary Sjögren's syndrome (SS), in 36, 38 and 56% of 45 patients with rheumatoid arthritis, and in 8, 5 and 3% of 40 normal controls. A high proportion of primary SS patients also had considerable amounts of serum...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(91)90016-6
更新日期:1991-02-01 00:00:00
abstract::Dysregulation of autophagy has been implicated in the development of various disease indications including autoimmune diseases. Here we identified hitherto unsuspected molecular alterations of autophagy occurring at an early stage of the macroautophagy pathway in the salivary glands and spleen of NOD.H-2h4 mice that d...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102418
更新日期:2020-03-01 00:00:00