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https://www.readbyqxmd.com/read/28720143/mhc-class-ii-expression-and-potential-antigen-presenting-cells-in-the-retina-during-experimental-autoimmune-uveitis
#1
Deborah A Lipski, Rémi Dewispelaere, Vincent Foucart, Laure E Caspers, Matthieu Defrance, Catherine Bruyns, François Willermain
BACKGROUND: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. METHODS: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals...
July 18, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716943/visualizing-context-dependent-calcium-signaling-in-encephalitogenic-t-cells-in-vivo-by-two-photon-microscopy
#2
Nikolaos I Kyratsous, Isabel J Bauer, Guokun Zhang, Marija Pesic, Ingo Bartholomäus, Marsilius Mues, Ping Fang, Miriam Wörner, Stephanie Everts, Joachim W Ellwart, Joanna M Watt, Barry V L Potter, Reinhard Hohlfeld, Hartmut Wekerle, Naoto Kawakami
In experimental autoimmune encephalitis (EAE), autoimmune T cells are activated in the periphery before they home to the CNS. On their way, the T cells pass through a series of different cellular milieus where they receive signals that instruct them to invade their target tissues. These signals involve interaction with the surrounding stroma cells, in the presence or absence of autoantigens. To portray the serial signaling events, we studied a T-cell-mediated model of EAE combining in vivo two-photon microscopy with two different activation reporters, the FRET-based calcium biosensor Twitch1 and fluorescent NFAT...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28709864/the-role-of-human-natural-killer-1-hnk-1-carbohydrate-in-neuronal-plasticity-and-disease
#3
REVIEW
Jyoji Morise, Hiromu Takematsu, Shogo Oka
BACKGROUND: The human natural killer-1 (HNK-1) carbohydrate, a unique trisaccharide possessing sulfated glucuronic acid in a non-reducing terminus (HSO3-3GlcAß1-3Galß1-4GlcNAc-), is highly expressed in the nervous system and its spatiotemporal expression is strictly regulated. Mice deficient in the gene encoding a key enzyme, GlcAT-P, of the HNK-1 biosynthetic pathway exhibit almost complete disappearance of the HNK-1 epitope in the brain, significant reduction of long-term potentiation, and aberration of spatial learning and memory formation...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28709804/identification-of-natural-regulatory-t-cell-epitopes-reveals-convergence-on-a-dominant-autoantigen
#4
John D Leonard, Dana C Gilmore, Thamotharampillai Dileepan, Wioletta I Nawrocka, Jaime L Chao, Mary H Schoenbach, Marc K Jenkins, Erin J Adams, Peter A Savage
Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell clones, one prevalent in prostate tumors and the other associated with prostatic autoimmune lesions, recognized distinct non-overlapping MHC-class-II-restricted peptides derived from the same prostate-specific protein...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28705779/autoimmune-aspects-of-psoriasis-heritability-and-autoantigens
#5
REVIEW
Jörg Christoph Prinz
Chronic immune-mediated disorders (IMDs) constitute a major health burden. Understanding IMD pathogenesis is facing two major constraints: Missing heritability explaining familial clustering, and missing autoantigens. Pinpointing IMD risk genes and autoimmune targets, however, is of fundamental importance for developing novel causal therapies. The strongest association of all IMDs is seen with human leukocyte antigen (HLA) alleles. Using psoriasis as an IMD model this article reviews the pathogenic role HLA molecules may have within the polygenic predisposition of IMDs...
July 10, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28701761/antigen-specific-immunotherapies-in-rheumatic-diseases
#6
REVIEW
Judit Pozsgay, Zoltán Szekanecz, Gabriella Sármay
The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative - disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence...
July 13, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28694810/oxidized-hemoglobin-is-antigenic-and-immunogenic-in-lupus
#7
Sonia Jain, Anjali Bose, Banajit Bastia, Hritika Sharma, Ruchi Sachdeva, Arun K Jain, Rahul Pal
Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunological consequences, particularly in the context of pre-existing lupus. IgG anti-Hb responses were detected in the sera of lupus patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric (Fe(3+)) Hb triggered preferential release of lupus-associated cytokines from splenocytes derived from aging lupus-prone mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28694505/presence-of-diabetes-autoantigens-in-extracellular-vesicles-derived-from-human-islets
#8
Craig P Hasilo, Sarita Negi, Isabelle Allaeys, Nathalie Cloutier, Alissa K Rutman, Marco Gasparrini, Éric Bonneil, Pierre Thibault, Éric Boilard, Steven Paraskevas
Beta-cell (β-cell) injury is the hallmark of autoimmune diabetes. However, the mechanisms by which autoreactive responses are generated in susceptible individuals are not well understood. Extracellular vesicles (EV) are produced by mammalian cells under normal and stressed physiological states. They are an important part of cellular communication, and may serve a role in antigen processing and presentation. We hypothesized that isolated human islets in culture produce EV that contain diabetes autoantigens (DAA) from these otherwise normal, non-diabetic donors...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687989/screening-novel-autoantigens-targeted-by-serum-igg-autoantibodies-in-immunorelated-pancytopenia-by-serex
#9
Shanfeng Hao, Rong Fu, Huaquan Wang, Zonghong Shao
Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated destruction or suppression of bone marrow. However, the autoantigens targeted by autoantibodies in IRP remain unclear. In the present study, we screened novel autoantigens in IRP by serological analysis of recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels between IRP and normal controls detected by immunoblotting. Our results indicate that we successfully constructed the K562 cDNA library, which we used to screen seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin, light polypeptide, ubiquinol-cytochrome c reductase, complex III subunit X (UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform 1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3, phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex subunit 4 (TRAPPC4)...
July 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28686485/impaired-salivary-gland-activity-in-patients-with-autoimmune-polyendocrine-syndrome-type-i
#10
Bergithe E Oftedal, Mihaela Cuida Marthinussen, Martina M Erichsen, Maria K Tveitarås, Anja Kjellesvik-Kristiansen, Daniel Hammenfors, Malin V Jonsson, Kai Kisand, Roland Jonsson, Anette S B Wolff
Autoimmune polyendocrine syndrome type I (APS-I) is a severe disease caused by mutations in the autoimmune regulator (AIRE) gene. We hypothesized that salivary gland dysfunction could be a possible unexplored component of these patients and here aimed to investigate salivary and lachrymal symptoms in the Norwegian cohort of APS-I patients (N = 41) and the aetiology behind it. Sicca symptoms and possible corresponding underlying factors were assessed by subjective reports combined with objective measures of saliva and tear flow, serological testing, immune fluorescence microscopy, ultrasonography and searching for putative autoantibodies in the salivary glands...
July 7, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28680335/analysis-of-the-autoimmune-response-against-bp180-and-bp230-in-ethnic-poles-with-neurodegenerative-disorders-and-bullous-pemphigoid
#11
Justyna Gornowicz-Porowska, Agnieszka Seraszek-Jaros, Monika Bowszyc-Dmochowska, Elżbieta Kaczmarek, Paweł Pietkiewicz, Paweł Bartkiewicz, Marian Dmochowski
Recent studies postulated the association between bullous pemphigoid (BP) and neurodegenerative disorders (ND). The autoantibodies to BP180 and/or BP230 may be present not only in BP, but also in ND as neuronal isoforms of these proteins are identified in the central nervous system. However, there are only scant data about the precise pathogenetic mechanisms interlinking ND and BP as well as the immunologic profile in these patients. The aim is to analyze the serological immunopathological profiles (anti-BP180 IgG, anti-BP230 IgG) in BP patients with and without ND in order to identify the specific autoantibody(ies) and corresponding antigens responsible for ND development in BP patients...
2017: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/28677172/neurological-and-psychiatric-associations-in-bullous-pemphigoid-more-than-skin-deep
#12
REVIEW
Anna-Kaisa Försti, Laura Huilaja, Enno Schmidt, Kaisa Tasanen
In elderly patients, bullous pemphigoid (BP) is associated with several comorbidities; the strongest association occurs between BP and neurological diseases. Different types of dementia, Parkinson's disease, cerebrovascular disorders and epilepsy all have a significant association with BP but patients with multiple sclerosis have the highest risk of BP. An existing neurological disorder appears to increase the risk for subsequent BP, but an increased risk for developing some neurological diseases has also been reported following BP diagnosis...
July 4, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28674893/serum-profiling-for-identification-of-autoantibody-signatures-in-diseases-using-protein-microarrays
#13
Shabarni Gupta, K P Manubhai, Shuvolina Mukherjee, Sanjeeva Srivastava
Protein microarrays are platforms for studying protein-protein interactions and identifying disease-related self-antigens/autoantigens, which elicit an immune response in a high-throughput format. Protein arrays have been extensively used over the past two decades for several clinical applications. By using this platform, serum containing autoantibodies against potential self-antigens can be screened on proteome-wide arrays, harboring a large repertoire of full-length human proteins. Identification of such autoantigens can help deducing early diagnostic, as well as, prognostic markers in case of malignancies, autoimmune disorders, and other systemic diseases...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674210/chinese-medicine-ginseng-and-astragalus-granules-ameliorate-autoimmune-diabetes-by-upregulating-both-cd4-foxp3-and-cd8-cd122-pd1-regulatory-t-cells
#14
Yeshu Wang, Qingfeng Xie, Chun-Ling Liang, Qiaohuang Zeng, Zhenhua Dai
Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28674044/pla2r-and-thsd7a-disparate-paths-to-the-same-disease
#15
REVIEW
Laurence H Beck
The phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major autoantigens in primary membranous nephropathy (MN), and define two molecular subclasses of this disease. Both proteins are large transmembrane glycoproteins expressed by the podocyte, and both induce IgG4-predominant humoral immune responses that produce circulating autoantibodies that can be used clinically for diagnostic and monitoring purposes. The biologic roles of these proteins remain speculative, although several features of THSD7A suggest a role in adhesion...
July 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28669815/immuno-proteomic-discovery-of-tumor-tissue-autoantigens-identifies-olfactomedin-4-cd11b-and-integrin-alpha-2-as-markers-of-colorectal-cancer-with-liver-metastases
#16
Qian Yang, Prashant Bavi, Julia Y Wang, Michael H Roehrl
Late-stage colorectal cancer with liver metastasis is common and affords poor prognosis, yet there is a dearth of reliable biomarkers. Cancer is often characterized by an increase in serologic autoantibodies. Hence, we embarked on an immuno-proteomic strategy by using autoantibodies to discover antigens in tumor tissue as potential cancer markers. Matched sets of tissues from primary colon cancer, liver metastases, and adjacent benign tissues were obtained from colon cancer patients. Tissue proteins were extracted, and autoantigens were uncovered by immunoblotting with autoantibodies and sequenced by mass spectrometry...
June 29, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28667526/isolation-of-natural-anti-fc%C3%AE%C2%B5ri%C3%AE-autoantibodies-from-healthy-donors
#17
Monique Vogel, Michael P Horn
Natural antibodies are defined as antibodies detected in a healthy individual without active immunization. These antibodies are specific for exoantigens, as well as for autoantigens, mostly without any pathogenic role. Most of the studies conducted with natural (auto-) antibodies have been performed using affinity purified antibodies from individual sera or polyclonal Ig-preparations such as Intravenous Ig (IVIg). For in-depth analysis of such autoantibodies affinity-purified Ig-preparations from healthy individuals are of no use, as they are oligoclonal or polyclonal...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28665492/antigen-presenting-cell-targeted-proinsulin-expression-converts-insulin-specific-cd8-t-cell-priming-to-tolerance-in-autoimmune-prone-nod-mice
#18
Peta L S Reeves, Rajeev Rudraraju, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing pancreatic β cells. Therapies need to incorporate strategies to overcome the genetic defects that impair induction or maintenance of peripheral T-cell tolerance and contribute to disease development. We tested whether the enforced expression of an islet autoantigen in antigen-presenting cells (APC) counteracted peripheral T-cell tolerance defects in autoimmune-prone NOD mice. We observed that insulin-specific CD8(+) T cells transferred to mice in which proinsulin was transgenically expressed in APCs underwent several rounds of division and the majority were deleted...
June 30, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28655516/characterization-of-autoantigen-presentation-by-hla-c-06-02-in-psoriasis
#19
Pengcheng Wei, Yi Yang, Zhaoxin Liu, Zuoqin Luo, Wenya Tu, Junyan Han, Yunhua Deng, Lei Yin
No abstract text is available yet for this article.
June 24, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28650341/two-rheumatoid-arthritis-specific-autoantigens-correlate-microbial-immunity-with-autoimmune-responses-in-joints
#20
Annalisa Pianta, Sheila L Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels...
June 26, 2017: Journal of Clinical Investigation
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