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https://www.readbyqxmd.com/read/28805301/the-lymphocytes-stimulation-induced-dna-release-a-phenomenon-similar-to-netosis
#1
Yermis Carolina Rocha, Mauricio Rojas, Gloria Vásquez, Juan López
The release of DNA into the extracellular milieu by neutrophil during a process called NETosis has been postulated as an additional source of autoantigens; a process believed to be important in the pathogenesis of some autoimmune disease, such as Systemic Lupus Erythematosus (SLE). However, it is not established if the B and T cells undergo the release of DNA to the extracellular milleu, in response to different stimuli. In this study, it was observed that, the treatment of B and T cells with PMA, ionomycin, and the serum from patients with SLE induced the extracellular DNA presence in B and T cells...
August 11, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28804903/targeting-of-tolerogenic-dendritic-cells-towards-heat-shock-proteins-a-novel-therapeutic-strategy-for-autoimmune-diseases
#2
REVIEW
Manon A A Jansen, Rachel Spiering, Femke Broere, Jacob M van Laar, John D Isaacs, Willem van Eden, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T cell response, while leaving other, protective T cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen...
August 14, 2017: Immunology
https://www.readbyqxmd.com/read/28794553/vitamin-d-level-in-alopecia-areata
#3
Yasmeen Jabeen Bhat, Insha Latif, Rauf Malik, Iffat Hassan, Gousia Sheikh, Kouser Sideeq Lone, Sabiya Majeed, Peerzada Sajad
BACKGROUND: Alopecia areata (AA) is an immune-mediated disease in which autoantigens play an important part in activating T-lymphocytes. Vitamin D has been associated with various autoimmune diseases, and Vitamin D receptors are strongly expressed in hair follicles and their expression in keratinocytes is necessary for the maintenance of the normal hair cycle. AIM: The aim of this study was to find the association between Vitamin D level and AA. MATERIALS AND METHODS: This was a hospital-based cross-sectional study in which 50 patients with clinically and trichoscopically diagnosed AA cases, and 35 healthy age- and sex-matched controls were studied in summer months...
July 2017: Indian Journal of Dermatology
https://www.readbyqxmd.com/read/28794283/metabolic-and-immune-effects-of-immunotherapy-with-proinsulin-peptide-in-human-new-onset-type-1-diabetes
#4
Mohammad Alhadj Ali, Yuk-Fun Liu, Sefina Arif, Danijela Tatovic, Hina Shariff, Vivienne B Gibson, Norkhairin Yusuf, Roman Baptista, Martin Eichmann, Nedyalko Petrov, Susanne Heck, Jennie H M Yang, Timothy I M Tree, Irma Pujol-Autonell, Lorraine Yeo, Lucas R Baumard, Rachel Stenson, Alex Howell, Alison Clark, Zoe Boult, Jake Powrie, Laura Adams, Florence S Wong, Stephen Luzio, Gareth Dunseath, Kate Green, Alison O'Keefe, Graham Bayly, Natasha Thorogood, Robert Andrews, Nicola Leech, Frank Joseph, Sunil Nair, Susan Seal, HoYee Cheung, Craig Beam, Robert Hills, Mark Peakman, Colin M Dayan
Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28783661/citrullination-of-nf-%C3%AE%C2%BAb-p65-promotes-its-nuclear-localization-and-tlr-induced-expression-of-il-1%C3%AE-and-tnf%C3%AE
#5
Bo Sun, Nishant Dwivedi, Tyler J Bechtel, Janet L Paulsen, Aaron Muth, Mandar Bawadekar, Gang Li, Paul R Thompson, Miriam A Shelef, Celia A Schiffer, Eranthie Weerapana, I-Cheng Ho
Many citrullinated proteins are known autoantigens in rheumatoid arthritis, a disease mediated by inflammatory cytokines, such as tumor necrosis factor-α (TNFα). Citrullinated proteins are generated by converting peptidylarginine to peptidylcitrulline, a process catalyzed by the peptidylarginine deiminases (PADs), including PAD1 to PAD4 and PAD6. Several major risk factors for rheumatoid arthritis are associated with heightened citrullination. However, the physiological role of citrullination in immune cells is poorly understood...
June 9, 2017: Science Immunology
https://www.readbyqxmd.com/read/28780731/unmet-needs-in-the-field-of-psoriasis-pathogenesis-and-treatment
#6
REVIEW
Wolf-Henning Boehncke, Nicolo Costantino Brembilla
In times of targeted therapies, innovative therapeutics become tools to further unravel the pathogenesis of the treated disease, thus influencing current pathogenetic concepts. Based on such paradigm shifts, the next generation of novel therapeutic targets might be identified. Psoriasis is a good example for the resulting most fruitful dialog between clinical and fundamental research. As a result of this, the key role of Th17 lymphocytes, some of their effector molecules, as well as mediators contributing to their maturation have been identified, many of these being targeted by some of the most effective drugs currently available to treat psoriasis...
August 6, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28774715/dendritic-cell-recruitment-and-activation-in-autoimmunity
#7
REVIEW
Silvano Sozzani, Annalisa Del Prete, Daniela Bosisio
Dendritic cells (DCs) are professional antigen presenting cells displaying the unique capability to activate naïve T cells. DCs react to pathogen encounter also by the production of mediators of inflammation, including pro-inflammatory cytokines. Because of this complex role, any imbalance in DC function reflects into defective or exaggerated immune response and tissue damage. DCs comprise two main subsets, namely conventional or classical DCs (cDCs), that are dedicated antigen presenting cells, and plasmacytoid DCs (pDCs), that respond to nucleic acids by releasing high amounts of type I interferons (IFNs)...
July 31, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28772271/remission-phase-in-paediatric-type-1-diabetes-new-understanding-and-emerging-biomarkers
#8
Mireia Fonolleda, Marta Murillo, Federico Vázquez, Joan Bel, Marta Vives-Pi
Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children...
August 3, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28770318/regulatory-t-cell-dysfunction-in-type-1-diabetes-what-s-broken-and-how-can-we-fix-it
#9
REVIEW
Caroline M Hull, Mark Peakman, Timothy I M Tree
Type 1 diabetes is an autoimmune disease characterised by the destruction of insulin producing beta cells in the pancreas. Whilst it remains unclear what the original triggering factors for this destruction are, observations from the natural history of human type 1 diabetes, including incidence rates in twins, suggest that the disease results from a combination of genetic and environmental factors. Whilst many different immune cells have been implicated, including members of the innate and adaptive immune systems, a view has emerged over the past 10 years that beta cell damage is mediated by the combined actions of CD4(+) and CD8(+) T cells with specificity for islet autoantigens...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28761156/aggravation-of-collagen-induced-arthritis-by-orally-administered-porphyromonas-gingivalis-through-modulation-of-the-gut-microbiota-and-gut-immune-system
#10
Keisuke Sato, Naoki Takahashi, Tamotsu Kato, Yumi Matsuda, Mai Yokoji, Miki Yamada, Takako Nakajima, Naoki Kondo, Naoto Endo, Reiko Yamamoto, Yuichiro Noiri, Hiroshi Ohno, Kazuhisa Yamazaki
Porhyromonas gingivalis, a causative bacterium of periodontitis, is implicated in the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl arginine deiminase (PAD) that generates RA-related autoantigens. However, compared with other periodontopathic bacteria, the precise role of P. gingivalis in RA is largely unknown. We found that orally administered P. gingivalis changed the gut microbiome with concomitant elevation of serum endotoxin and inflammatory markers, and impairment of the gut barrier function...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761078/the-complement-system-a-gateway-to-gene-environment-interactions-in-schizophrenia-pathogenesis
#11
V L Nimgaonkar, K M Prasad, K V Chowdari, E G Severance, R H Yolken
The pathogenesis of schizophrenia is considered to be multi-factorial, with likely gene-environment interactions (GEI). Genetic and environmental risk factors are being identified with increasing frequency, yet their very number vastly increases the scope of possible GEI, making it difficult to identify them with certainty. Accumulating evidence suggests a dysregulated complement pathway among the pathogenic processes of schizophrenia. The complement pathway mediates innate and acquired immunity, and its activation drives the removal of damaged cells, autoantigens and environmentally derived antigens...
August 1, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28755952/are-humans-prone-to-autoimmunity-implications-from-evolutionary-changes-in-hominin-sialic-acid-biology
#12
REVIEW
Ajit Varki
Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity...
July 26, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28754682/autoimmunity-to-vimentin-is-associated-with-outcomes-of-patients-with-idiopathic-pulmonary-fibrosis
#13
Fu Jun Li, Ranu Surolia, Huashi Li, Zheng Wang, Tejaswini Kulkarni, Gang Liu, Joao A de Andrade, Daniel J Kass, Victor J Thannickal, Steven R Duncan, Veena B Antony
Autoimmunity has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF); however, the repertoire of autoantigens involved in this disease and the clinical relevance of these autoimmune responses are still being explored. Our initial discovery assays demonstrated that circulating and intrapulmonary vimentin levels are increased in IPF patients. Subsequent studies showed native vimentin induced HLA-DR-dependent in vitro proliferation of CD4 T cells from IPF patients and enhanced the production of IL-4, IL-17, and TGF-β1 by these lymphocytes in contrast to normal control specimens...
July 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28753623/solution-nmr-structure-of-the-trim21-b-box2-and-identification-of-residues-involved-in-its-interaction-with-the-ring-domain
#14
Amélie Wallenhammar, Madhanagopal Anandapadamanaban, Alexander Lemak, Claudio Mirabello, Patrik Lundström, Björn Wallner, Maria Sunnerhagen
Tripartite motif-containing (TRIM) proteins are defined by the sequential arrangement of RING, B-box and coiled-coil domains (RBCC), where the B-box domain is a unique feature of the TRIM protein family. TRIM21 is an E3 ubiquitin-protein ligase implicated in innate immune signaling by acting as an autoantigen and by modifying interferon regulatory factors. Here we report the three-dimensional solution structure of the TRIM21 B-box2 domain by nuclear magnetic resonance (NMR) spectroscopy. The structure of the B-box2 domain, comprising TRIM21 residues 86-130, consists of a short α-helical segment with an N-terminal short β-strand and two anti-parallel β-strands jointly found the core, and adopts a RING-like fold...
2017: PloS One
https://www.readbyqxmd.com/read/28753571/1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol-ameliorates-arthritic-joints-through-reducing-neutrophil-infiltration-mediated-by-il-6-stat3-and-mip-2-activation
#15
Young-Jun Kim, Jae Min Shin, Su-Hyun Shin, Joo Heon Kim, Ki-Young Sohn, Heung-Jae Kim, Jong-Koo Kang, Sun Young Yoon, Jae Wha Kim
The pathogenesis of rheumatoid arthritis (RA) has been implicated neutrophil extracellular traps (NETs) formation which could generate autoantigen. Neutrophil contributes to initiate and maintain the inflammatory process in the joint. In this study, we show that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) decreases neutrophil migration by regulating the activity of STAT3, a regulator of IL-6 and MIP-2 expression. PLAG caused a decrease in IL-6 production in the RAW264.7 macrophage cell line and in rheumatoid arthritis-fibroblast-like synoviocytes via the regulation of STAT3 signaling without affecting NF-κB signaling...
July 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752717/justification-for-ige-as-a-therapeutic-target-in-chronic-spontaneous-urticaria
#16
M Sánchez-Borges, A Capriles-Hulet, F Caballero-Fonseca, L González-Aveledo
Monoclonal anti-IgE antibodies (omalizumab) are able to induce clinically significant benefits in patients with severe chronic spontaneous urticaria (CS). Those results led clinicians and investigators to reconsider a possible pathogenic role not previously supported for IgE and its receptors in this disease, and to investigate additional approaches for understanding its pathogenesis. IgE antibodies to unknown environmental allergens able to trigger chronic urticaria are not generally regarded as the etiologic factor for the disease...
July 2017: European Annals of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28751821/immunomodulation-of-ra-patients-pbmc-with-a-multiepitope-peptide-derived-from-citrullinated-autoantigens
#17
Smadar Gertel, Gidi Karmon, Sivan Vainer, Ora Shovman, Martin Cornillet, Guy Serre, Yehuda Shoenfeld, Howard Amital
Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME) from the sequences of major citrullinated autoantigens: filaggrin, β-fibrinogen, vimentin, and collagen type II...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28748216/t-cells-targeting-neuromyelitis-optica-autoantigen-aquaporin-4-cause-paralysis-and-visual-system-injury
#18
COMMENT
Andrés Cruz-Herranz, Sharon A Sagan, Raymond A Sobel, Ari J Green, Scott S Zamvil
Aquaporin-4 (AQP4)-specific antibodies are instrumental in promoting central nervous system (CNS) tissue injury in neuromyelitis optica (NMO), yet evidence indicates that AQP4-specific T cells also have a pivotal role in NMO pathogenesis. Although considerable effort has been devoted to creation of animal models to study how AQP4-specific T cells and antibodies may cooperate in development of both clinical and histologic opticospinal inflammatory disease, the initial attempts were unsuccessful. Recently, it was discovered that T cells from AQP4-deficient (AQP4(-/-)) mice recognize distinct AQP4 epitopes that were not identified previously in wild-type (WT) mice, and that donor Th17 cells from AQP4(-/-) mice that target those novel epitopes could cause paralysis and visual system injury associated with opticospinal inflammation in WT recipient mice...
May 2017: Journal of Nature and Science
https://www.readbyqxmd.com/read/28746384/detection-of-brain-directed-autoantibodies-in-the-serum-of-non-small-cell-lung-cancer-patients
#19
Manoj Banjara, Chaitali Ghosh, Aaron Dadas, Peter Mazzone, Damir Janigro
Antibodies against brain proteins were identified in the plasma of cancer patients and are defined to cause paraneoplastic neurological syndromes. The profiles of brain-directed antibodies in non-small cell lung cancer (NSCLC) are largely unknown. Here, for the first time, we compared autoantibodies against brain proteins in NSCLC (n = 18) against those present in age-matched non-cancer control subjects (n = 18) with a similar life-style, habit, and medical history. Self-recognizing immunoglobulin (IgG) are primarily directed against cells in the cortex (P = 0...
2017: PloS One
https://www.readbyqxmd.com/read/28745995/intralymphatic-injection-of-autoantigen-in-type-1-diabetes
#20
(no author information available yet)
New England Journal of Medicine, Volume 377, Issue 4, Page 405-405, July 2017.
July 27, 2017: New England Journal of Medicine
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