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https://www.readbyqxmd.com/read/28326907/skin-sensitizers-in-cosmetics-and-beyond-potential-multiple-mechanisms-of-action-and-importance-of-t-cell-assays-for-in-vitro-screening
#1
Stanislav Vukmanović, Nakissa Sadrieh
Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity (DTH) reaction induced by repeated contact with sensitizers. The ability of a chemical to act as a sensitizer has most frequently been tested in animals. As the use of animals for these purposes is gradually and globally being phased out, there is a need for reliable in vitro surrogate assays. Currently proposed in vitro assays are designed to test four key events of the adverse outcome pathway (AOP) involving covalent modification of self-proteins by sensitizers (haptenation) and presentation of new antigens (hapten/carrier complexes) to the immune system...
March 22, 2017: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/28320282/extracellular-actin-in-health-and-disease
#2
REVIEW
N P Sudakov, I V Klimenkov, V A Byvaltsev, S B Nikiforov, Yu M Konstantinov
This review considers the functions of extracellular actin - cell surface bound, associated with extracellular matrix, or freely circulating. The role of this protein in different pathological processes is analyzed: its toxic effects and involvement in autoimmune diseases as an autoantigen. The extracellular actin clearance system and its role in protection against the negative effects of actin are characterized. Levels of free-circulating actin, anti-actin immunoglobulins, and components of the actin clearance system as prognostic biomarkers for different diseases are reviewed...
January 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28318808/t-cell-receptor-assessment-in-autoimmune-disease-requires-access-to-the-most-adjacent-immunologically-active-organ
#3
Bergithe E Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R Holdsworth, Christopher N Hahn, Andreas W Schreiber, Hamish S Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs...
March 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28314223/gv1001-immunotherapy-ameliorates-joint-inflammation-in-a-murine-model-of-rheumatoid-arthritis-by-modifying-collagen-specific-t-cell-responses-and-downregulating-antigen-presenting-cells
#4
In Ah Choi, Ji Yong Choi, Sundo Jung, Fathihah Basri, Seho Park, Eun Young Lee
This study investigated whether GV1001 may be useful for treating rheumatoid arthritis (RA). Two collagen-induced arthritis (CIA) experiments showed that therapeutic, but not preventive, GV1001 treatment reduced the severity of joint inflammation in CIA. The third CIA experiment indicated that, compared to vehicle treatment, therapeutic GV1001 treatment was associated with a significantly smaller area under the curve for the overall clinical joint score over the 98day observation period (p<0.05). GV1001 treatment was also associated with lower Day 98 serum IL-6 levels (p<0...
March 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28300427/annexin-a1-as-a-target-for-managing-murine-pristane-induced-systemic-lupus-erythematosus
#5
Nikolina Mihaylova, Silviya Bradyanova, Petroslav Chipinski, Melinda Herbáth, Stela Chausheva, Dobroslav Kyurkchiev, József Prechl, Andrey I Tchorbanov
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy...
March 16, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28300170/cd8-t-cells-specific-for-the-islet-autoantigen-igrp-are-restricted-in-their-t-cell-receptor-chain-usage
#6
Yannick F Fuchs, Anne Eugster, Sevina Dietz, Christian Sebelefsky, Denise Kühn, Carmen Wilhelm, Annett Lindner, Anita Gavrisan, Jan Knoop, Andreas Dahl, Anette-G Ziegler, Ezio Bonifacio
CD8(+) T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8(+) T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8(+) T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer(+) CD8(+) T cells representing 48 clonotypes were obtained...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298564/proteomic-analysis-of-sera-from-individuals-with-diffuse-cutaneous-systemic-sclerosis-reveals-a-multianalyte-signature-associated-with-clinical-improvement-during-imatinib-mesylate-treatment
#7
D James Haddon, Hannah E Wand, Justin A Jarrell, Robert F Spiera, Paul J Utz, Jessica K Gordon, Lorinda S Chung
OBJECTIVE: Imatinib has been investigated for the treatment of systemic sclerosis (SSc) because of its ability to inhibit the platelet-derived growth factor receptor and transforming growth factor-β signaling pathways, which have been implicated in SSc pathogenesis. In a 12-month open-label clinical trial assessing the safety and efficacy of imatinib in the treatment of diffuse cutaneous SSc (dcSSc), significant improvements in skin thickening were observed. Here, we report our analysis of sera collected during the clinical trial...
March 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28298428/autoantibodies-to-synaptic-receptors-and-neuronal-cell-surface-proteins-in-autoimmune-diseases-of-the-central-nervous-system
#8
REVIEW
Josep Dalmau, Christian Geis, Francesc Graus
Investigations in the last 10 years have revealed a new category of neurological diseases mediated by antibodies against cell surface and synaptic proteins. There are currently 16 such diseases all characterized by autoantibodies against neuronal proteins involved in synaptic signaling and plasticity. In clinical practice these findings have changed the diagnostic and treatment approach to potentially lethal, but now treatable, neurological and psychiatric syndromes previously considered idiopathic or not even suspected to be immune-mediated...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28291659/identification-of-carbamylated-alpha-1-anti-trypsin-a1at-as-an-antigenic-target-of-anti-carp-antibodies-in-patients-with-rheumatoid-arthritis
#9
Marije K Verheul, Alvin Yee, Andrea Seaman, George M Janssen, Peter A van Veelen, Jan W Drijfhout, Rene E M Toes, Michael Mahler, Leendert A Trouw
In 2011 a novel autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, was described in rheumatoid arthritis (RA) patients. Anti-CarP antibody positivity associates with a more severe disease course, is observed years before disease onset, and may predict the development of RA in arthralgia patients. Although many clinical observations have been carried out, information on the antigenic targets of anti-CarP antibodies is limited. Most studies on anti-CarP antibodies utilize an ELISA-based assay with carbamylated fetal calf serum (Ca-FCS) as antigen, a complex mixture of proteins...
March 10, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28287110/t-cells-and-autoimmune-kidney-disease
#10
REVIEW
Abel Suárez-Fueyo, Sean J Bradley, David Klatzmann, George C Tsokos
Glomerulonephritis is traditionally considered to result from the invasion of the kidney by autoantibodies and immune complexes from the circulation or following their formation in situ, and by cells of the innate and the adaptive immune system. The inflammatory response leads to the proliferation and dysfunction of cells of the glomerulus, and invasion of the interstitial space with immune cells, resulting in tubular cell malfunction and fibrosis. T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity against kidney resident cells...
March 13, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28274366/pemphigus-vulgaris-and-pemphigus-foliaceus-determined-by-cd86-and-ctla4-polymorphisms
#11
Srdjan Tanasilovic, Svetlana Popadic, Ljiljana Medenica, Dusan Popadic
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare autoimmune blistering diseases with presumed T-cell-dependent pathology. Activation of naïve T cells is dependent on antigen recognition, subsequent signaling through the T-cell receptor complex (signal 1), and various other interactions of T cells with antigen presenting cells that may be collectively designated as signal 2, which is unconditionally required for T-cell activation both in response to infection and to autoantigens. Among the best described interactions contributing to signal 2 are those mediated by B7 family molecules, such as CD80 and CD86 with their ligands; CD28, providing activation signals; and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), conferring inhibition...
March 2017: Clinics in Dermatology
https://www.readbyqxmd.com/read/28273770/transglutaminase-6-is-an-autoantigen-in-progressive-multiple-sclerosis-and-is-upregulated-in-reactive-astrocytes
#12
Massimiliano Cristofanilli, Daniel Gratch, Benjamin Pagano, Kelsey McDermott, Jessie Huang, Jeffrey Jian, Deneb Bates, Saud A Sadiq
BACKGROUND: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. OBJECTIVE: To investigate TGM6 involvement in multiple sclerosis (MS). METHODS: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28271685/the-expression-of-b7-h3-in-circulating-cd4-cd25high-t-cells-circulating-cd14-monocytes-and-plasma-during-hepatitis-b-virus-infection-progression
#13
Jun-Chi Xu, Ming Li, Yuan Ma, Cui-Lin Shi, Xiao-Yan Zhu, Hua-Feng Song, Hui Chen, Chuan-Wu Zhu, Ping Xu
BACKGROUND: B7-H3 is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, the role of B7-H3 which express in CD14+ monocytes and CD4+CD25high T cells had not been investigated. METHODS: Cytometry and ELISA were used in this study. RESULTS: The study showed that B7-H3 expression in CD14+ monocytes, CD4+CD25high T cells, and plasma was significantly increased in AHB, CHB, HBV-LC, and HBV-HCC group...
March 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28270614/engineered-erythrocytes-covalently-linked-to-antigenic-peptides-can-protect-against-autoimmune-disease
#14
Novalia Pishesha, Angelina M Bilate, Marsha C Wibowo, Nai-Jia Huang, Zeyang Li, Rhogerry Dhesycka, Djenet Bousbaine, Hojun Li, Heide C Patterson, Stephanie K Dougan, Takeshi Maruyama, Harvey F Lodish, Hidde L Ploegh
Current therapies for autoimmune diseases rely on traditional immunosuppressive medications that expose patients to an increased risk of opportunistic infections and other complications. Immunoregulatory interventions that act prophylactically or therapeutically to induce antigen-specific tolerance might overcome these obstacles. Here we use the transpeptidase sortase to covalently attach disease-associated autoantigens to genetically engineered and to unmodified red blood cells as a means of inducing antigen-specific tolerance...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28266741/signaling-and-targeted-therapy-of-inflammatory-cells-in-epidermolysis-bullosa-acquisita
#15
REVIEW
Ralf J Ludwig
Pemphigoid diseases (PD) are chronic and life-threating autoimmune diseases of the skin and mucous membranes. PD are characterized and caused by autoantibodies targeting components of the basement membrane. In the PD epidermolysis bullosa acquisita (EBA) the target autoantigen is type VII collagen. Current treatment options of PD, especially EBA, are limited and are mostly based on systemic immunosuppression. Animal models of PD have greatly advanced our understanding of PD pathogenesis. This has led to the identification of several novel therapeutic targets, including signaling molecules...
March 7, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28256368/checkpoint-based-immunotherapy-for-autoimmune-diseases-opportunities-and-challenges
#16
EDITORIAL
Xiao-Song He, M Eric Gershwin, Aftab A Ansari
Immune checkpoint pathways modulate the T cell response to ensure their dual function in maintaining health, eradicating or controlling malignancy and infection, as well as tolerating host autoantigens. Dysregulation of the checkpoint pathways may lead to development of cancer or persistent infection, or alternately, autoimmune diseases. Currently available treatments for autoimmune diseases, such as steroid and nonsteroid immunosuppressive medicines, have limited efficacy. Checkpoint-based immunotherapy, designed to directly block the activation pathway or agitate the inhibitory pathway of autoreactive T cells, is a promising therapeutic strategy for restoring T cell tolerance in autoimmune diseases...
February 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28255003/prognostic-value-of-serum-biomarkers-of-autoimmunity-for-recurrence-of-iga-nephropathy-after-kidney-transplantation
#17
Francois Berthoux, Hitoshi Suzuki, Hesham Mohey, Nicolas Maillard, Christophe Mariat, Jan Novak, Bruce A Julian
A prognostic biomarker for IgA nephropathy (IgAN) recurrence after renal transplant is lacking. We followed 96 consecutive first renal transplant recipients with native kidney IgAN (79 men; 92 deceased donors; mean age =48.1 years old) on calcineurin inhibitor-based immunosuppression over 10 years for death, allograft failure, and clinicopathologic recurrence (CPR; clinically evident and biopsy proven). Using time-dependent Cox regression analysis and receiver operating characteristic curves, we assessed prognostic significance of levels of galactose-deficient IgA1 (Gd-IgA1; autoantigen) and Gd-IgA1-specific IgG and IgA autoantibodies in serum obtained at time of transplant or native kidney IgAN diagnosis (30 patients only)...
March 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28250776/allogeneic-adipose-derived-mesenchymal-stromal-cells-ameliorate-experimental-autoimmune-encephalomyelitis-by-regulating-self-reactive-t-cell-responses-and-dendritic-cell-function
#18
Per Anderson, Elena Gonzalez-Rey, Francisco O'Valle, Francisco Martin, F Javier Oliver, Mario Delgado
Multipotent mesenchymal stromal cells (MSCs) have emerged as a promising therapy for autoimmune diseases, including multiple sclerosis (MS). Administration of MSCs to MS patients has proven safe with signs of immunomodulation but their therapeutic efficacy remains low. The aim of the current study has been to further characterize the immunomodulatory mechanisms of adipose tissue-derived MSCs (ASCs) in vitro and in vivo using the EAE model of chronic brain inflammation in mice. We found that murine ASCs (mASCs) suppress T cell proliferation in vitro via inducible nitric oxide synthase (iNOS) and cyclooxygenase- (COX-) 1/2 activities...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28248292/potassium-channels-kv1-3-and-kca3-1-cooperatively-and-compensatorily-regulate-antigen-specific-memory-t-cell-functions
#19
Eugene Y Chiang, Tianbo Li, Surinder Jeet, Ivan Peng, Juan Zhang, Wyne P Lee, Jason DeVoss, Patrick Caplazi, Jun Chen, Søren Warming, David H Hackos, Susmith Mukund, Christopher M Koth, Jane L Grogan
Voltage-gated Kv1.3 and Ca(2+)-dependent KCa3.1 are the most prevalent K(+) channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3...
March 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28244336/characterisation-of-the-nucleic-acid-binding-features-of-the-prrsv-7ap-and-its-ability-to-induce-antinuclear-antibodies
#20
Ferenc Olasz, Béla Dénes, Ádám Bálint, Tibor Magyar, Sándor Belák, Zoltán Zádori
A short alternative open reading frame named ORF7a has recently been discovered within the nucleocapsid gene of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. Proteins (7ap) translated from the ORF7a of two divergent strains - a type I and a type II - are able to completely reduce the motility of nucleic acids at relatively high molar charge ratios in gel retardation assays indicating strong dsDNA- and ssRNA-binding capability. Conserved RNA- and DNA-binding properties suggest that nucleic acid binding is a functional property of the divergent 7aps, and not an arbitrary consequence of their net positive charge...
March 2017: Acta Veterinaria Hungarica
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