A Spectrum of Neural Autoantigens, Newly Identified by Histo-Immunoprecipitation, Mass Spectrometry, and Recombinant Cell-Based Indirect Immunofluorescence.

Abstract:

Background:A plurality of neurological syndromes is associated with autoantibodies against neural antigens relevant for diagnosis and therapy. Identification of these antigens is crucial to understand the pathogenesis and to develop specific immunoassays. Using an indirect immunofluorescence assay (IFA)-based approach and applying different immunoprecipitation (IP), chromatographic and mass spectrometric protocols was possible to isolate and identify a spectrum of autoantigens from brain tissue. Methods:Sera and CSF of 320 patients suspected of suffering from an autoimmune neurological syndrome were comprehensively investigated for the presence of anti-neural IgG autoantibodies by IFA using mosaics of biochips with brain tissue cryosections and established cell-based recombinant antigen substrates as well as immunoblots. Samples containing unknown brain tissue-specific autoantibodies were subjected to IP with cryosections of cerebellum and hippocampus (rat, pig, and monkey) immobilized to glass slides or with lysates produced from homogenized tissue, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, tryptic digestion, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis. Identifications were confirmed by IFA with recombinant HEK293 cells and by neutralizing the patients' autoantibodies with the respective recombinantly expressed antigens in the tissue-based immunofluorescence test. Results:Most samples used in this study produced speckled, granular, or homogenous stainings of the hippocampal and cerebellar molecular and/or granular layers. Others exclusively stained the Purkinje cells. Up to now, more than 20 different autoantigens could be identified by this approach, among them ATP1A3, CPT1C, Flotillin1/2, ITPR1, NBCe1, NCDN, RGS8, ROCK2, and Syntaxin-1B as novel autoantigens. Discussion:The presented antigen identification strategy offers an opportunity for identifying up to now unknown neural autoantigens. Recombinant cell substrates containing the newly identified antigens can be used in serology and the clinical relevance of the autoantibodies can be rapidly evaluated in cohort studies.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Scharf M,Miske R,Kade S,Hahn S,Denno Y,Begemann N,Rochow N,Radzimski C,Brakopp S,Probst C,Teegen B,Stöcker W,Komorowski L

doi

10.3389/fimmu.2018.01447

subject

Has Abstract

pub_date

2018-07-09 00:00:00

pages

1447

issn

1664-3224

journal_volume

9

pub_type

杂志文章
  • P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis.

    abstract::Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IP...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01028

    authors: Müller T,Fay S,Vieira RP,Karmouty-Quintana H,Cicko S,Ayata CK,Zissel G,Goldmann T,Lungarella G,Ferrari D,Di Virgilio F,Robaye B,Boeynaems JM,Lazarowski ER,Blackburn MR,Idzko M

    更新日期:2017-08-22 00:00:00

  • Proapoptotic BIM Impacts B Lymphoid Homeostasis by Limiting the Survival of Mature B Cells in a Cell-Autonomous Manner.

    abstract::The proapoptotic BH3-only protein BIM (Bcl2l11) plays key roles in the maintenance of multiple hematopoietic cell types. In mice, germline knockout or conditional pan-hematopoietic deletion of Bim results in marked splenomegaly and significantly increased numbers of B cells. However, it has remained unclear whether th...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00592

    authors: Liu R,King A,Bouillet P,Tarlinton DM,Strasser A,Heierhorst J

    更新日期:2018-03-22 00:00:00

  • Functional Annotation of Genetic Loci Associated With Sepsis Prioritizes Immune and Endothelial Cell Pathways.

    abstract::Due to limited sepsis patient cohort size and extreme heterogeneity, only one significant locus and suggestive associations at several independent loci were implicated by three genome-wide association studies. However, genes from such suggestive loci may also provide crucial information to unravel genetic mechanisms t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01949

    authors: Le KTT,Matzaraki V,Netea MG,Wijmenga C,Moser J,Kumar V

    更新日期:2019-08-14 00:00:00

  • Synergy between Common γ Chain Family Cytokines and IL-18 Potentiates Innate and Adaptive Pathways of NK Cell Activation.

    abstract::Studies to develop cell-based therapies for cancer and other diseases have consistently shown that purified human natural killer (NK) cells secrete cytokines and kill target cells after in vitro culture with high concentrations of cytokines. However, these assays poorly reflect the conditions that are likely to prevai...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00101

    authors: Nielsen CM,Wolf AS,Goodier MR,Riley EM

    更新日期:2016-03-22 00:00:00

  • Role of Dendritic Cells in Natural Immune Control of HIV-1 Infection.

    abstract::Dendritic cells (DCs) are professional antigen-presenting cells that link innate and adaptive immunity and are critical for the induction of protective immune responses against pathogens. Proportions of these cells are markedly decreased in the blood of untreated HIV-1-infected individuals, suggesting they might be in...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01306

    authors: Martin-Gayo E,Yu XG

    更新日期:2019-06-06 00:00:00

  • The Inflammatory Role of Platelets via Their TLRs and Siglec Receptors.

    abstract::Platelets are non-nucleated cells that play central roles in the processes of hemostasis, innate immunity, and inflammation; however, several reports show that these distinct functions are more closely linked than initially thought. Platelets express numerous receptors and contain hundreds of secretory products. These...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00083

    authors: Cognasse F,Nguyen KA,Damien P,McNicol A,Pozzetto B,Hamzeh-Cognasse H,Garraud O

    更新日期:2015-03-02 00:00:00

  • Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates.

    abstract::All animals develop in association with complex microbial communities. It is now well established that commensal microbiota is essential for the correct functionality of each organ in the host. Particularly, the commensal gastro-intestinal microbiota (CGIM) is a key factor for development, immunity and nutrient conver...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00512

    authors: Montalban-Arques A,De Schryver P,Bossier P,Gorkiewicz G,Mulero V,Gatlin DM 3rd,Galindo-Villegas J

    更新日期:2015-10-09 00:00:00

  • Double Positive CD4+CD8+ T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization.

    abstract::The immune system plays a central role in cancer development, showing both anti-tumor and pro-tumor activities depending on the immune cell subsets and the disease context. While CD8 T cells are associated with a favorable outcome in most cancers, only T helper type 1 (Th1) CD4 T cells play a protective role, in contr...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章

    doi:10.3389/fimmu.2019.00622

    authors: Bohner P,Chevalier MF,Cesson V,Rodrigues-Dias SC,Dartiguenave F,Burruni R,Tawadros T,Valerio M,Lucca I,Nardelli-Haefliger D,Jichlinski P,Derré L

    更新日期:2019-03-29 00:00:00

  • Pseudomonas aeruginosa Modulates the Antiviral Response of Bronchial Epithelial Cells.

    abstract::Cystic fibrosis (CF) patients frequently acquire Pseudomonas aeruginosa infections that have been associated with a bad prognosis and an increased rate of pulmonary exacerbations. Respiratory viruses can cause exacerbations in chronic pulmonary diseases including COPD or asthma and have been suggested to contribute to...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00096

    authors: Sörensen M,Kantorek J,Byrnes L,Boutin S,Mall MA,Lasitschka F,Zabeck H,Nguyen D,Dalpke AH

    更新日期:2020-02-04 00:00:00

  • CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter.

    abstract::CD28 is an important co-stimulatory receptor for T lymphocytes that, in humans, delivers TCR-independent signal leading to the up-regulation of pro-inflammatory cytokines. We have recently reported that CD28 autonomous signaling induces the expression of IL-17A in peripheral CD4+ T lymphocytes from healthy donors, mul...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00864

    authors: Kunkl M,Mastrogiovanni M,Porciello N,Caristi S,Monteleone E,Arcieri S,Tuosto L

    更新日期:2019-04-24 00:00:00

  • Dendritic Epidermal T Cells in Allergic Contact Dermatitis.

    abstract::Allergic contact dermatitis (ACD) is a common inflammatory skin disease with a prevalence of approximately 20% in the European population. ACD is caused by contact allergens that are reactive chemicals able to modify non-immunogenic self-proteins to become immunogenic proteins. The most frequent contact allergens are ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00874

    authors: Mraz V,Geisler C,Bonefeld CM

    更新日期:2020-05-19 00:00:00

  • High-Speed Single-Molecule Tracking of CXCL13 in the B-Follicle.

    abstract::Soluble factors are an essential means of communication between cells and their environment. However, many molecules readily interact with extracellular matrix components, giving rise to multiple modes of diffusion. The molecular quantification of diffusion in situ is thus a challenging imaging frontier, requiring ver...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01073

    authors: Miller H,Cosgrove J,Wollman AJM,Taylor E,Zhou Z,O'Toole PJ,Coles MC,Leake MC

    更新日期:2018-05-22 00:00:00

  • The Complexity of Fungal β-Glucan in Health and Disease: Effects on the Mononuclear Phagocyte System.

    abstract::β-glucan, the most abundant fungal cell wall polysaccharide, has gained much attention from the scientific community in the last few decades for its fascinating but not yet fully understood immunobiology. Study of this molecule has been motivated by its importance as a pathogen-associated molecular pattern upon fungal...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.00673

    authors: Camilli G,Tabouret G,Quintin J

    更新日期:2018-04-16 00:00:00

  • CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8α+ and CD8α- Conventional Dendritic Cell Subsets.

    abstract::Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01727

    authors: Antonialli R,Sulczewski FB,Amorim KNDS,Almeida BDS,Ferreira NS,Yamamoto MM,Soares IS,Ferreira LCS,Rosa DS,Boscardin SB

    更新日期:2017-12-04 00:00:00

  • Intravital Microscopic Evaluation of the Effects of a CXCR2 Antagonist in a Model of Liver Ischemia Reperfusion Injury in Mice.

    abstract:Background:Ischemia-reperfusion (IR) is a major contributor to graft rejection after liver transplantation. During IR injury, an intense inflammatory process occurs in the liver. Neutrophils are considered central players in the events that lead to liver injury. CXC chemokines mediate hepatic inflammation following rep...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01917

    authors: de Oliveira THC,Marques PE,Poosti F,Ruytinx P,Amaral FA,Brandolini L,Allegretti M,Proost P,Teixeira MM

    更新日期:2018-01-05 00:00:00

  • Dried Blood Spots, an Affordable Tool to Collect, Ship, and Sequence gDNA from Patients with an X-Linked Agammaglobulinemia Phenotype Residing in a Developing Country.

    abstract:Background:New sequencing techniques have revolutionized the identification of the molecular basis of primary immunodeficiency disorders (PID) not only by establishing a gene-based diagnosis but also by facilitating defect-specific treatment strategies, improving quality of life and survival, and allowing factual genet...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00289

    authors: Segundo GRS,Nguyen ATV,Thuc HT,Nguyen LNQ,Kobayashi RH,Le HT,Le HTM,Torgerson TR,Ochs HD

    更新日期:2018-02-16 00:00:00

  • Natural Killer Cells and Type 1 Innate Lymphoid Cells Are New Actors in Non-alcoholic Fatty Liver Disease.

    abstract::Obesity and associated liver diseases (Non Alcoholic Fatty Liver Disease, NAFLD) are a major public health problem with increasing incidence in Western countries (25% of the affected population). These complications develop from a fatty liver (steatosis) to an inflammatory state (steatohepatitis) evolving toward fibro...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01192

    authors: Luci C,Vieira E,Perchet T,Gual P,Golub R

    更新日期:2019-05-28 00:00:00

  • A Method for Isolating and Culturing Skin Cells: Application to Endothelial Cells, Fibroblasts, Keratinocytes, and Melanocytes From Punch Biopsies in Systemic Sclerosis Skin.

    abstract::Systemic Sclerosis (SSc) is a complex auto-immune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin effectively recapitulates the main pathogenic processes and therefore is a good organ to decipher the disease pathophysiology, which remains unclear. However, culturing pr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.566607

    authors: Henrot P,Laurent P,Levionnois E,Leleu D,Pain C,Truchetet ME,Cario M

    更新日期:2020-10-07 00:00:00

  • Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing-Remitting-Multiple Sclerosis Patients.

    abstract:Background:Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing-remitting (RR) form, characterized by flare-ups followed by periods of recov...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01240

    authors: D'Angelo C,Reale M,Costantini E,Di Nicola M,Porfilio I,de Andrés C,Fernández-Paredes L,Sánchez-Ramón S,Pasquali L

    更新日期:2018-06-04 00:00:00

  • The Receptor for Advanced Glycation Endproducts Does Not Contribute to Pathology in a Mouse Mesenteric Ischemia/Reperfusion-Induced Injury Model.

    abstract::The receptor for advanced glycation endproducts (RAGE) can engage a diverse class of ligands and contribute to the immune and inflammatory response to infection and injury. It is known to be a pathogenic receptor in many inflammatory diseases, including ischemia/reperfusion (IR) injuries in several tissues; however, i...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00614

    authors: Wu MC,Gilmour TD,Mantovani S,Woodruff TM

    更新日期:2015-12-07 00:00:00

  • Analysis of the Interaction between Globular Head Modules of Human C1q and Its Candidate Receptor gC1qR.

    abstract::The heterotrimeric globular head (gC1q) domain of human C1q is made up of the C-terminal ends of the three individual chains, ghA, ghB, and ghC. A candidate receptor for the gC1q domain is a multi-functional pattern recognition protein, gC1qR. Since understanding of gC1qR and gC1q interaction could provide an insight ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00567

    authors: Pednekar L,Pathan AA,Paudyal B,Tsolaki AG,Kaur A,Abozaid SM,Kouser L,Khan HA,Peerschke EI,Shamji MH,Stenbeck G,Ghebrehiwet B,Kishore U

    更新日期:2016-12-13 00:00:00

  • Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections.

    abstract::Natural killer (NK) cells are the major innate effectors primed to eliminate virus-infected and tumor or neoplastic cells. Recent studies also suggest nuances in phenotypic and functional characteristics among NK cell subsets may further permit execution of regulatory and adaptive roles. Animal models, particularly no...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01124

    authors: Manickam C,Shah SV,Nohara J,Ferrari G,Reeves RK

    更新日期:2019-05-22 00:00:00

  • Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity.

    abstract::While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02555

    authors: Araujo Furlan CL,Tosello Boari J,Rodriguez C,Canale FP,Fiocca Vernengo F,Boccardo S,Beccaria CG,Adoue V,Joffre O,Gruppi A,Montes CL,Acosta Rodriguez EV

    更新日期:2018-11-05 00:00:00

  • The Role of the Immune Response in Chlamydia trachomatis Infection of the Male Genital Tract: A Double-Edged Sword.

    abstract::Chlamydia trachomatis (CT) is the most prevalent bacterial sexually transmitted infection in the world, with more than 100 million cases reported annually. While there have been extensive studies into the adverse effects that CT infection has on the female genital tract, and on the subsequent ability of these women to...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2014.00534

    authors: Redgrove KA,McLaughlin EA

    更新日期:2014-10-27 00:00:00

  • A Threshold Model for T-Cell Activation in the Era of Checkpoint Blockade Immunotherapy.

    abstract::Continued discoveries of negative regulators of inflammatory signaling provide detailed molecular insights into peripheral tolerance and anti-tumor immunity. Accumulating evidence indicates that peripheral tolerance is maintained at multiple levels of immune responses by negative regulators of proinflammatory signalin...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00491

    authors: Guram K,Kim SS,Wu V,Sanders PD,Patel S,Schoenberger SP,Cohen EEW,Chen SY,Sharabi AB

    更新日期:2019-03-18 00:00:00

  • The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses.

    abstract::The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses. However, these approach...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2016.00040

    authors: Mokhtar H,Pedrera M,Frossard JP,Biffar L,Hammer SE,Kvisgaard LK,Larsen LE,Stewart GR,Somavarapu S,Steinbach F,Graham SP

    更新日期:2016-02-16 00:00:00

  • G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets.

    abstract::Cytokines are known to shape the tumor microenvironment and although progress has been made in understanding their role in carcinogenesis, much remains to learn regarding their role in tumor growth and progression. We have identified granulocyte colony-stimulating factor (G-CSF) as one such cytokine, showing that G-CS...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01885

    authors: Karagiannidis I,Jerman SJ,Jacenik D,Phinney BB,Yao R,Prossnitz ER,Beswick EJ

    更新日期:2020-09-15 00:00:00

  • Intravital Multiphoton Microscopy of the Ocular Surface: Alterations in Conventional Dendritic Cell Morphology and Kinetics in Dry Eye Disease.

    abstract::Dry eye disease (DED) is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis and ocular symptoms, in which neurosensory abnormalities have recently been shown to play an etiological role. Although the role of inflammation has been widely studied in DED, the kinetics of immune...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00742

    authors: Jamali A,Seyed-Razavi Y,Chao C,Ortiz G,Kenyon B,Blanco T,Harris DL,Hamrah P

    更新日期:2020-05-07 00:00:00

  • The Joint-Brain Axis: Insights From Rheumatoid Arthritis on the Crosstalk Between Chronic Peripheral Inflammation and the Brain.

    abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nerv...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.612104

    authors: Süß P,Rothe T,Hoffmann A,Schlachetzki JCM,Winkler J

    更新日期:2020-12-10 00:00:00

  • Dopaminergic Stimulation of Myeloid Antigen-Presenting Cells Attenuates Signal Transducer and Activator of Transcription 3-Activation Favouring the Development of Experimental Autoimmune Encephalomyelitis.

    abstract::The dual potential to promote tolerance or inflammation to self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. Previous results have shown that stimulation of dopamine receptor D5 (DRD5) in DCs potentiates their inflammatory behaviour, favouring the development of experimental autoimmune enc...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00571

    authors: Prado C,Gaiazzi M,González H,Ugalde V,Figueroa A,Osorio-Barrios FJ,López E,Lladser A,Rasini E,Marino F,Zaffaroni M,Cosentino M,Pacheco R

    更新日期:2018-03-21 00:00:00