Search results for "Autoantigens"
showing 10 items of 121 documents
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
2016
Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encod…
Heterogeneity of circulating CD8 T-cells specific to islet, neo-antigen and virus in patients with type 1 diabetes mellitus
2018
Auto-reactive CD8 T-cells play an important role in the destruction of pancreatic β-cells resulting in type 1 diabetes (T1D). However, the phenotype of these auto-reactive cytolytic CD8 T-cells has not yet been extensively described. We used high-dimensional mass cytometry to phenotype autoantigen- (pre-proinsulin), neoantigen- (insulin-DRIP) and virus- (cytomegalovirus) reactive CD8 T-cells in peripheral blood mononuclear cells (PBMCs) of T1D patients. A panel of 33 monoclonal antibodies was designed to further characterise these cells at the single-cell level. HLA-A2 class I tetramers were used for the detection of antigen-specific CD8 T-cells. Using a novel Hierarchical Stochastic Neighb…
Exploring the MHC-peptide matrix of central tolerance in the human thymus
2013
Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class…
Immunological Effects of Allopurinol in the Treatment of Experimental Autoimmune Uveitis (EAU) after Onset of the Disease
2003
Purpose Allopurinol reduces oxidative tissue damage and exerts immunomodulating effects in the treatment of experimental autoimmune uveitis (EAU). However, the mechanism of the immunologic pathway remains unclear. In previous studies, treatment was started at the time of immunization. Therefore, whether allopurinol prevents the onset of the disease (i.e., acts in a protective manner) is not known. Methods Sixteen male Lewis rats were used: 6 EAU without therapy [control]; 4 EAU with allopurinol treatment starting 7 days after immunization [AL7]; and 6 EAU with allopurinol treatment starting 11 days after immunization [AL11]. Their sera were tested against Western blots of sodium dodecyl sul…
Complete congenital heart block is associated with increased autoantibody titers against calreticulin.
1996
Complete congenital heart block (CCHB) is associated with anti-Ro/SS-A and anti-La/SS-B antibodies. Calreticulin, a calcium-binding, multi-functional protein of the endoplasmic reticulum with C-terminal KDEL-sequence, is not part of the Ro/SS-A ribonucleoprotein complex. In this study anti-calreticulin autoantibody responses in serum samples from 18 infants with CCHB, their mothers and in a control group of 11 anti-Ro/SS-A or anti-La/SS-B positive infants without heart block and their mothers were analysed. Specific enzyme-linked immunosorbent assays were performed. Nine out of 18 sera with CCHB contained IgG anti-calreticulin antibodies. Four sera of those with IgG antibodies also had IgM …
Allopurinol has Immunomodulating Activity following Topical and Systemic Application in Experimental Autoimmune Uveitis
2001
PurposeAllopurinol has beneficial effects in the systemic treatment of lens-induced uveitis and experimental autoimmune uveitis (EAU). This is believed to be due to a reduction of oxidative tissue damage through its dose-dependent free radical scavenging ability, and to an immunomodulating effect. The purpose of this study was to demonstrate the immunological effects on the IgG-antibody repertoire in EAU after topical and systemic allopurinol and steroids.MethodsWe assigned 43 male Lewis rats to 6 different groups: healthy rats (BASE, n=3), EAU without therapy (CTRL, n=9); systemic treatment with allopurinol (ALSYS, n=9, 50 mg/kg body wt.i.v., given every three days for two weeks), topical …
Genetic association of autoimmune hepatitis and human leucocyte antigen in German patients
2006
To report on our large German collective and updated data of 142 patients with autoimmune hepatitis (AIH) type 1.Key investigations performed were liver biopsy, serum autoantibodies as well as serum markers such as IgG and elevated transaminases. Antinuclear antigen (ANA) and smooth muscle antigen (SMA) autoantibodies characterized type 1 AIH. Type 3 (AIH) was solely characterized by the occurrence of soluble liver antigen/liver-pancreas antigen (SLA/LP) autoantibodies either with or without ANA or SMA autoantibodies.Most prevalent HLAs were A2 (68 patients, 48%), B8 (63 patients, 44%), C7 (90 patients, 63%), DR3 (49 patients, 38%), DR4 (49 patients, 38%) and DQ2 (42 patients, 30%). Compare…
Identification of α-tubulin as an autoantigen recognized by sera from patients with neuropsychiatric systemic lupus erythematosus.
2011
In a previous study we found in 50% of patients with neuropsychiatric manifestations of systemic lupus erythematosus (NP-SLE) organ specific antibodies to 45-56 kD proteins in a 100,000 g supernatant (SN) from bovine brain mitochondria. Aim of the present study was to identify the corresponding target antigen. A 100,000 g SN from bovine brain mitochondria was applied to SDS-gel electrophoresis. A 50 kD band recognized by sera from patients with NP-SLE in the Western blot (WB) was excised from the gels and applied to mass spectrometry. The identified protein was expressed in Escherichia coli and retested against sera from eleven patients with NP-SLE (severe symptoms n=6, mild symptoms n=5), …
Upregulation of antibody response to heat shock proteins and tissue antigens in an ocular ischemia model.
2011
PURPOSE. The aim of this study was to characterize the serum antibody reactivities occurring after ocular ischemia reperfusion. The time course of serum antibody responses was examined. METHODS. Wistar rats were exposed to transient ocular ischemia by elevating intraocular pressure to 130 mm Hg for 60 minutes. Axonal damage was evaluated on optic-nerve sections 2 and 4 weeks later. Blood samples collected before and several times after ischemia were used for antibody detection via customized protein microarrays. Different tissue antigens, including heat shock proteins (HSPs) and crystallins, were selected based on previous identification of antibody reactivities in studies on ischemic event…