Abstract:
:Myasthenia gravis (MG) is a prototypical antibody-mediated disease characterized by muscle weakness and fatigability. Serum antibodies to the acetylcholine receptor and muscle-specific tyrosine kinase receptor (MuSK) are found in about 85% and 8% of patients respectively. We have previously shown that more than 70% of MG patients with MuSK antibodies share the HLA DQ5 allele. The aim of the present study was to analyze the T cell receptor (TCR) repertoire specific for recombinant human MuSK protein. We used the CDR3 TRBV-TRBJ spectratyping (immunoscope) to analyze the T cell response to MuSK from 13 DQ5+ MuSK-MG patients and from 7 controls (six DQ5+ MuSK negative subjects and one DQ5- DQ3+ MuSK positive patient). DQ5+ MuSK-MG patients but not controls used a restricted set of TCR VJ rearrangements in response to MuSK stimulation. One semiprivate (TRBV29-TRBJ2.5) rearrangement was found in 5/13 patients, while 4 other semiprivate (one in TRBV28-TRBJ2.1 and in TRBV3-TRBJ1.2, and two in TRBV28-TRBJ1.2) rearrangements were differently shared by 4/13 patients each and were absent in controls. When we sequenced the TRBV29-TRBJ2.5 rearrangement, we obtained 26 different sequences of the expected 130 bp length from 117 samples of the 5 positive patients: two common motifs GXGQET/TEHQET were shared in 4 patients as semiprivate motifs. Thus, the MuSK-specific T-cell response appears to be restricted in DQ5+ MuSK-MG patients, with a semiprivate repertoire including a common motif of TRBV29. This oligoclonal restriction of T cells will allow the identification of immunodominant epitopes in the antigen, providing therefore new tools for diagnosis and targeted therapy.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Marino M,Maiuri MT,Di Sante G,Scuderi F,La Carpia F,Trakas N,Provenzano C,Zisimopoulou P,Ria F,Tzartos SJ,Evoli A,Bartoccioni Edoi
10.1016/j.jaut.2013.12.007subject
Has Abstractpub_date
2014-08-01 00:00:00pages
113-21eissn
0896-8411issn
1095-9157pii
S0896-8411(13)00154-6journal_volume
52pub_type
杂志文章abstract::Class II antigens of the major histocompatibility complex (MHC) have a well-defined role in restricting cellular interactions and presenting processed antigen to T cells. In addition, a fundamental role for Class II antigens in cellular activation has been suggested, following studies demonstrating that Class II antig...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90133-9
更新日期:1989-06-01 00:00:00
abstract::Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. T...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,多中心研究
doi:10.1016/j.jaut.2020.102512
更新日期:2020-11-01 00:00:00
abstract::Previous studies on Spanish patients with Primary Biliary Cirrhosis (PBC) have shown extensive, disease-specific cross-reactivity between the 65-kDa heat shock protein (hsp65) of Mycobacterium gordonae and pyruvate dehydrogenase complex-E2 (PDC-E2), the major target of anti-mitochondrial antibody (AMA). Studies on a B...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2004.03.002
更新日期:2004-06-01 00:00:00
abstract::Interferon-gamma (IFN-gamma) is implicated as a mediator of islet beta-cell destruction in autoimmune, insulin-dependent diabetes mellitus (IDDM). Because interleukin 12 (IL-12) is a potent inducer of IFN-gamma production, we sought evidence implicating IL-12 in IDDM development. In the present study, we used a revers...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0084
更新日期:1996-10-01 00:00:00
abstract::The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8(+) T-cell lymphocytosis associated with a CD8(+) T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also ma...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2015.01.010
更新日期:2015-05-01 00:00:00
abstract::Glutamic acid decarboxylase (GAD) has been shown to exist as two isoforms with molecular weights of 65 kD (GAD65) and 67 kD (GAD67) in the central nervous system as well as in several non-neuronal tissues, including the pancreatic islets. Recently, this enzyme has been proposed as a key beta-cell autoantigen in insuli...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1996.0004
更新日期:1996-02-01 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::Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by necrotizing vasculitis with the presence of pathogenic ANCA. ANCA can potentially cause neutrophil activation and induce neutrophil extracellular traps (NETs), resulting in endothelial damage as well as activation of autoreacti...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2019.102390
更新日期:2020-03-01 00:00:00
abstract::In contrast to several previously published reports, we demonstrate by a variety of antibody assays that bovine serum albumin (BSA) is not antigenically cross-reactive with the 69-kDa islet cell autoantigen (ICA69). Fast protein liquid chromatography purified BSA and highly purified recombinant human ICA69 were used t...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1998.0199
更新日期:1998-06-01 00:00:00
abstract::The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have be...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1999.0346
更新日期:2000-02-01 00:00:00
abstract::Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown aetiology. The major hallmark of this disease is the presence of antibodies against nuclear components, including double-stranded (ds)DNA and histones. The disease affects different organs, particularly the skin, kidneys and the nervous system. ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/s0896-8411(02)00110-5
更新日期:2003-03-01 00:00:00
abstract::Systemic Lupus Erythematosus (SLE) is a multisystem disease characterized by an increase in the secretion of autoantibodies. The mechanisms of autoantibody-induced disease have not been clarified. 1,25-Dihydroxy-vitamin D3 (1,25-D3) is known to be important in the regulation of normal human lymphocyte functions. Among...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(89)90012-7
更新日期:1989-12-01 00:00:00
abstract::The La antigen is a highly conserved protein, originally defined by sera of patients with Sjögren's syndrome or systemic lupus erythematosus (SLE). In the present study, we have produced and characterized a monoclonal anti-la antibody derived from mice with experimental SLE. The induction of SLE in these mice was achi...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/s0896-8411(05)80037-x
更新日期:1990-12-01 00:00:00
abstract::Human beta 2-glycoprotein I is a heavily glycosylated plasma protein which has been implicated in the binding of antiphospholipid antibodies to negatively charged phospholipids; a process considered as an important risk factor for the development of thrombosis. We have solved the crystal structure of beta 2-glycoprote...
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::Natural autoantibodies (autoNAb) recognize self antigens and are an important component of the immune system, as species ranging from invertebrates to vertebrates have polyreactive IgM NAbs. In higher vertebrates, different polyreactive autoNAbs isotypes are also frequently encountered and autopolyreactive IgG NAbs ar...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2013.01.006
更新日期:2013-03-01 00:00:00
abstract::Most autoimmune diseases (AID) are linked to an imbalance between autoreactive effector T cells (Teffs) and regulatory T cells (Tregs). While blocking Teffs with immunosuppression has long been the only therapeutic option, activating/expanding Tregs may achieve the same objective without the toxicity of immunosuppress...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jaut.2015.01.001
更新日期:2015-04-01 00:00:00
abstract::Bullous pemphigoid (BP) and linear IgA disease (LAD) are autoimmune subepidermal blistering skin diseases associated with autoantibodies against the transmembrane hemidesmosomal protein BP180/type XVII collagen. It has been demonstrated previously that BP is characterized predominantly by IgG autoantibodies, while aut...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.2000.0437
更新日期:2000-11-01 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::Very little is known about the cellular immune response in c-ANCA (classical anti-neutrophil cytoplasm antibodies) positive vasculitides or Wegener's granulomatosis (WG). The present review is mainly based on published and unpublished observations of the Cattegat Study Group of Wegener's Granulomatosis. Immunohistoche...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1006/jaut.1993.1020
更新日期:1993-04-01 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::To study the expression of protein tyrosine phosphatases (PTPs) in pancreatic islets, a cDNA library from islet cells was constructed and analysed. Twenty-one different PTPs were found to be expressed in islet cells, including three previously unknown PTPs. One of these, IA-2beta, was cloned, sequenced, and found to b...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1006/jaut.1997.0132
更新日期:1997-06-01 00:00:00
abstract::The use of autoantigen-specific regulatory T cells (Tregs) as a cellular therapy for autoimmune diseases is appealing. However, it is challenging to isolate and expand large quantity of Tregs expressing disease-relevant T-cell receptors (TCR). To overcome this problem, we used an approach aiming at redirecting the spe...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2020.102401
更新日期:2020-03-01 00:00:00
abstract::The interaction over time of genetic, epigenetic and environmental factors (i.e., autoimmune ecology) increases or decreases the liability an individual would have to develop an autoimmune disease (AD) depending on the misbalance between risk and protective effects. Pathogens have been the most common antecedent event...
journal_title:Journal of autoimmunity
pub_type: 杂志文章,评审
doi:10.1016/j.jaut.2019.06.012
更新日期:2019-09-01 00:00:00
abstract::Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previ...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/0896-8411(92)90187-u
更新日期:1992-12-01 00:00:00
abstract::Experimental autoimmune encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS), is dependent upon the activation and effector functions of autoreactive CD4 T cells. Multiple interactions between CD4 T cells and major histocompatibility class II (MHCII)+ antigen presenting cells (APCs) must occu...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2010.10.006
更新日期:2011-02-01 00:00:00
abstract::The probability that epitope spreading occurs in multiple sclerosis (MS) and the fact that patients have been shown to respond to multiple myelin epitopes concurrently makes the use of peptide-specific tolerance therapies targeting single epitopes problematic. To attempt to overcome this limitation, we have employed c...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2006.12.002
更新日期:2006-12-01 00:00:00
abstract::The induction and persistence of a hypo-inflammatory and immunosuppressive state in severe sepsis is commonly associated with increased risks of secondary infections and mortality. Toll-like receptor (TLR)-triggered inflammatory response of macrophages/monocytes plays an important role in determining the outcome of hy...
journal_title:Journal of autoimmunity
pub_type: 杂志文章
doi:10.1016/j.jaut.2017.04.006
更新日期:2017-07-01 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::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::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