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https://www.readbyqxmd.com/read/30337146/structural-mapping-of-hot-spots-within-human-caspr2-discoidin-domain-for-autoantibody-recognition
#1
Wenjun Liang, Junying Zhang, Margaux Saint-Martin, Fei Xu, Nelly Noraz, Jianmei Liu, Jérôme Honnorat, Heli Liu
Accumulating evidence has showed that anti-CASPR2 autoantibodies occur in a long list of neurological immune disorders including limbic encephalitis (LE). Belonging to the well-known neurexin superfamily, CASPR2 has been suggested to be a central node in the molecular networks controlling neurodevelopment. Distinct from other subfamilies in the neurexin superfamily, the CASPR subfamily features a unique discoidin (Disc) domain. As revealed by our and others' recent studies, CASPR2 Disc domain bears a major epitope for autoantibodies...
October 15, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/30283395/biomarkers-of-neurodegeneration-in-autoimmune-mediated-encephalitis
#2
Peter Körtvelyessy, Harald Prüss, Lorenz Thurner, Walter Maetzler, Deborah Vittore-Welliong, Jörg Schultze-Amberger, Hans-Jochen Heinze, Dirk Reinhold, Frank Leypoldt, Stephan Schreiber, Daniel Bittner
Progranulin (PGRN), Total-Tau (t-tau), and Neurofilament light chain (NfL) are well known biomarkers of neurodegeneration. The objective of the present study was to investigate whether these parameters represent also biomarkers in autoimmune-mediated Encephalitis (AE) and may give us insights into the pathomechanisms of AE. We retrospectively examined the concentration of PGRN in the cerebrospinal fluid (CSF) and serum of 38 patients suffering from AE in acute phase and/or under treatment. This AE cohort comprises patients with autoantibodies against: NMDAR ( n = 18 patients), Caspr2 ( n = 8), Lgi-1 ( n = 10), GABAB(R) ( n = 1), and AMPAR ( n = 1)...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/30265368/association-of-antibodies-against-myelin-and-neuronal-antigens-with-neuroinflammation-in-systemic-lupus-erythematosus
#3
Anne-Katrin Pröbstel, Madlaina Thanei, Barbara Erni, Anne-Catherine Lecourt, Léonore Branco, Raphaël André, Pascal Roux-Lombard, Katrin F Koenig, Uyen Huynh-Do, Camillo Ribi, Carlo Chizzolini, Ludwig Kappos, Marten Trendelenburg, Tobias Derfuss
Objectives: To determine frequency and syndrome specificity of novel and known nervous system (NS)-directed antibodies in a large, unbiased cohort of SLE patients in the Swiss SLE Cohort Study. Methods: This retrospective pilot study included 174 patients in a cross-sectional and 102 in a longitudinal study. Antibodies against 12 NS antigens [myelin oligodendrocyte glycoprotein (MOG), neurofascin 186 (NF186), aquaporin-4 (AQP4), N-methyl-D-aspartate receptor (subunit NR1) (NMDAR-NR1), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (subunits 1 and 2) (AMPAR1/2), gamma-aminobutyric acid B receptor (subunits B1 and B2) (GABABR1/2), glutamate decarboxylase 65 (GAD65), glycine receptor (GlyR), contactin-associated protein-like 2 (CASPR2), leucine-rich glioma-inactivated 1 (LGI1), metabotropic glutamate receptor 5 (mGluR5) and dipeptidyl-peptidase-like protein 6 (DPPX)] were screened with validated cell-based assays and correlated with clinical and diagnostic findings...
September 27, 2018: Rheumatology
https://www.readbyqxmd.com/read/30242309/association-of-leucine-rich-glioma-inactivated-protein-1-contactin-associated-protein-2-and-contactin-2-antibodies-with-clinical-features-and-patient-reported-pain-in-acquired-neuromyotonia
#4
Angela Vincent, Philippa Pettingill, Rosie Pettingill, Bethan Lang, Ron Birch, Patrick Waters, Sarosh R Irani, Camilla Buckley, Osamu Watanabe, Kimiyoshi Arimura, Matthew C Kiernan
Importance: Although acquired autoimmune neuromyotonia (NMT) is associated with voltage-gated potassium channel (VGKC)-complex antibodies, to date there has been no systematic study of autoantibodies to the specific antigens leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein 2 (CASPR2), and contactin 2 together with the full clinical syndrome, particularly pain and autonomic and central nervous system involvement. Objectives: To study the full spectrum of clinical features and serum autoantibodies in patients with NMT, including the effects of pain on quality of life...
September 17, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/30224548/pain-and-the-immune-system-emerging-concepts-of-igg-mediated-autoimmune-pain-and-immunotherapies
#5
Min Xu, David L H Bennett, Luis Antonio Querol, Long-Jun Wu, Sarosh R Irani, James C Watson, Sean J Pittock, Christopher J Klein
The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability...
September 17, 2018: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/30189384/neuronal-surface-antibody-mediated-encephalopathy-as-manifestation-of-chronic-graft-versus-host-disease-after-allogeneic-hematopoietic-stem-cell-transplantation
#6
Michelle Pirotte, Florence Forte, Laurence Lutteri, Evelyne Willems, Unal Duran, Ludovic Belle, Frédéric Baron, Yves Beguin, Pierre Maquet, Olivier Bodart, Sophie Servais
Although it remained controversial for a long time, central nervous system (CNS) involvement of graft-versus-host disease (GVHD) is now becoming recognized as a real nosological entity. Previous case reports have suggested heterogeneous clinical presentations and it is not excluded that the whole spectrum of manifestations has not yet been fully described. Here, we report the case of a 58-year-old man with chronic GVHD who developed a rapidly ingravescent encephalopathy. There was no evidence for CNS immune-mediated lesions on conventional imaging nor for cellular infiltration in the cerebrospinal fluid...
October 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/30146688/mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis-is-infrequently-associated-with-neuronal-autoantibodies
#7
Adaucto W Nóbrega-Jr, Christian P Gregory, Rachel Schlindwein-Zanini, Fabricio de Souza Neves, Peter Wolf, Roger Walz, Mario Steindel, Katia Lin
Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is characterized by its well-defined clinical profile. Limbic encephalitis is increasingly recognized as a possible etiology of adult-onset MTLE-HS, and neuronal autoantibodies have been detected in patients even without previous signs of encephalitis. The aim of this study is to analyze the frequency of specific autoantibodies in patients with MTLE-HS. A case-control study was carried out with 100 patients with MTLE-HS and 50 healthy controls...
September 2018: Epilepsia
https://www.readbyqxmd.com/read/30103974/distinction-between-anti-vgkc-complex-seropositive-patients-with-and-without-anti-lgi1-caspr2-antibodies
#8
Tianrong Yeo, Zhiyong Chen, Kok Pin Yong, Patricia Yut Wan Wong, Josiah Yui Huei Chai, Kevin Tan
BACKGROUND: To identify clinical and paraclinical differences between anti-voltage-gated potassium channel (VGKC)-complex seropositive patients with and without anti-leucine-rich glioma-inactivated protein 1 (LGI1)/contactin-associated protein-like 2 (CASPR2) antibodies (Abs). METHODS: We performed a retrospective analysis of 50 anti-VGKC-complex seropositive patients from January 2013 to September 2016, and tested them for anti-LGI1/CASPR2 Abs. Comparative analysis was performed between anti-LGI1/CASPR2 seropositive and 'double negative' patients...
August 15, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/30090985/morvan-s-syndrome-is-a-pathogen-behind-the-curtain
#9
Rohit Singh, Pritam Das, Upinder Kaur, Anamika Misra, Ashis Choudhury, Sukdev Manna, Rohit Gaude, Deepak Gautam, Indrajeet Singh Gambhir, Sankha Shubhra Chakrabarti
Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating delirium with prominent hallucinations. Since its first mention in 1890, less than 100 cases have been described in literature. The largest existing review includes details of 29 cases. This case series describes 4 cases (M = 4) of Morvan's syndrome which presented between May and November 2017 to a single tertiary care referral teaching hospital in north India...
August 9, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/30076629/lgi1-and-caspr2-neurological-autoimmunity-in-children
#10
A Sebastian López-Chiriboga, Christopher Klein, Anastasia Zekeridou, Andrew McKeon, Divyanshu Dubey, Eoin P Flanagan, Vanda A Lennon, Jan-Mendelt Tillema, Elaine C Wirrell, Marc C Patterson, Avi Gadoth, J Gregory Aaen, J Nicholas Brenton, Jonathan D Bui, Amanda Moen, Catherine Otten, Amanda Piquet, Sean J Pittock
The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3)...
September 2018: Annals of Neurology
https://www.readbyqxmd.com/read/30028556/contactin-associated-protein-like-2-a-protein-of-the-neurexin-family-involved-in-several-human-diseases
#11
REVIEW
Margaux Saint-Martin, Bastien Joubert, Véronique Pellier-Monnin, Olivier Pascual, Nelly Noraz, Jérôme Honnorat
Contactin-associated protein-like 2 (CASPR2) is a cell adhesion protein of the neurexin family. Proteins of this family have been shown to play a role in the development of the nervous system, in synaptic functions, and in neurological diseases. Over recent years, CASPR2 function has gained an increasing interest as demonstrated by the growing number of publications. Here, we gather published data to comprehensively review CASPR2 functions within the nervous system in relation to CASPR2-related diseases in humans...
August 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29954343/autoantibodies-against-neuronal-surface-proteins-in-spontaneous-subarachnoid-and-intracerebral-haemorrhage
#12
Harald Hegen, Raimund Helbok, Mario Kofler, Bettina Pfausler, Alois Schiefecker, Erich Schmutzhard, Ronny Beer
BACKGROUND: Brain autoimmunity has been reported in patients with preceding infection of the central nervous system by herpesviridae. It has been hypothesized that neuronal damage releasing antigens might trigger secondary immune response. The objective of the study was to investigate whether brain damage due to spontaneous subarachnoid haemorrhage (SAH) or intracerebral haemorrhage (ICH) induces reactivity against neuronal surface proteins. METHODS: Patients with spontaneous SAH and ICH, who had cerebrospinal fluid (CSF) and serum sampling within 2 weeks after disease onset (baseline) and afterwards at least 10 days later (follow-up), were included...
June 28, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29951031/evaluation-of-clinical-and-paraclinical-findings-for-the-differential-diagnosis-of-autoimmune-and-infectious-encephalitis
#13
Judith N Wagner, Ognian Kalev, Michael Sonnberger, Ingomar Krehan, Tim J von Oertzen
Background: The differential diagnosis of autoimmune and infectious encephalitis is notoriously difficult. For this study, we compare the presenting clinical symptoms and paraclinical test results of autoimmune and infectious encephalitis patients. A clinical algorithm for the diagnosis of autoimmune encephalitis has recently been published. We test these Graus criteria on our cohort for diagnostic sensitivity and specificity within the first week of presentation. Methods: We included all patients seen at our department within a 10-year-period who were diagnosed with encephalitis...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29788256/distinct-hla-associations-of-lgi1-and-caspr2-antibody-diseases
#14
Sophie Binks, James Varley, Wanseon Lee, Mateusz Makuch, Katherine Elliott, Jeffrey M Gelfand, Saiju Jacob, M Isabel Leite, Paul Maddison, Mian Chen, Michael D Geschwind, Eleanor Grant, Arjune Sen, Patrick Waters, Mark McCormack, Gianpiero L Cavalleri, Martin Barnardo, Julian C Knight, Sarosh R Irani
The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies...
May 18, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29788201/genetic-variants-in-autism-related-cntnap2-impair-axonal-growth-of-cortical-neurons
#15
Giorgia Canali, Marta Garcia, Bruno Hivert, Delphine Pinatel, Aline Goullancourt, Ksenia Oguievetskaia, Margaux Saint-Martin, Jean-Antoine Girault, Catherine Faivre-Sarrailh, Laurence Goutebroze
The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro...
June 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29774053/postherpes-simplex-encephalitis-a-case-series-of-viral-triggered-autoimmunity-synaptic-autoantibodies-and-response-to-therapy
#16
Harry Alexopoulos, Sofia Akrivou, Sotiria Mastroyanni, Maria Antonopoulou, Argirios Dinopoulos, Melpo Giorgi, Kostas Konstantinou, Evangelos Kouremenos, Maria Lariou, Dimitrios Naoumis, Efterpi Pavlidou, Evaggelos Pavlou, Konstantinos Voudris, Panayotis Vlachoyiannopoulos, Marinos C Dalakas
Background: Recent evidence suggests that patients with herpes simplex virus (HSV) encephalitis may relapse because of autoimmunity against the N-methyl-D-aspartate receptor (NMDAR). We present a case series of post-HSV relapsing encephalopathy associated with antibodies to central nervous system (CNS) synaptic antigens. Patient/Methods: Sera and cerebrospinal fluid (CSF) from five patients with HSV encephalitis who relapsed after antiviral therapy were tested for anti-NMDAR, gamma-aminobutyric acid b receptor (GABAbR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), Leucine-rich, glioma inactivated 1 (LGI1), anti -contactin-associated protein-like 2 (CASPR2) and dipeptidyl-peptidase-like protein-6 (DDPX) antibodies using cell-based assays...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29761119/antibodies-against-cell-adhesion-molecules-and-neural-structures-in-paraneoplastic-neuropathies
#17
Ana M Siles, Eugenia Martínez-Hernández, Josefa Araque, Jordi Diaz-Manera, Ricard Rojas-Garcia, Eduard Gallardo, Isabel Illa, Francesc Graus, Luis Querol
Objective: Paraneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN). Methods: Thirty-four patients fulfilling diagnostic criteria of possible ( n = 9; 26...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29720798/mercury-toxicity-following-unauthorized-siddha-medicine-intake-a-mimicker-of-acquired-neuromyotonia-report-of-32-cases
#18
G Gnanashanmugam, R Balakrishnan, S P Somasundaram, N Parimalam, P Rajmohan, M B Pranesh
Context: Mercury is used extensively in the preparation of Siddha medicines, after purification. In this study, we present 32 patients of mercury toxicity following unauthorized Siddha medicine intake who mimicked neuromyotonia clinically. We analyzed the clinical features of these patients, the role of autoimmunity in etiopathology, and compared it with acquired neuromyotonia. Subjects and Methods: This is a retrospective study to analyze inpatients in a tertiary care center, admitted with mercury toxicity following Siddha medicine intake from August 2012 to October 2016...
January 2018: Annals of Indian Academy of Neurology
https://www.readbyqxmd.com/read/29610228/video-neuroimages-paraneoplastic-spinal-myoclonus-associated-with-caspr2-antibodies
#19
Harrison Hines, Nick M Murray, Sarah Ahmad, Safwan Jaradeh, Carl A Gold
No abstract text is available yet for this article.
April 3, 2018: Neurology
https://www.readbyqxmd.com/read/29561731/paraneoplastic-movement-disorders
#20
Karolina Popławska-Domaszewicz, Jolanta Florczak-Wyspiańska, Wojciech Kozubski, Sławomir Michalak
Paraneoplastic movement disorders are rare, autoimmune-mediated, nonmetastatic complications of malignant neoplasms. Common paraneoplastic movement disorders include paraneoplastic chorea, dystonia, cerebellar degeneration, different types of encephalitis, opsoclonus-myoclonus syndrome, stiff person syndrome, and neuromyotonia. Syndromes usually develop before tumor diagnosis, have subacute onset, and are associated with serum or cerebrospinal fluid antibodies. Two types of antibodies can be distinguished: antibodies against nuclear and cytoplasmic neuronal antigens (anti-Hu, anti-Ri, anti-Yo, anti-Ma, anti-CV2/CRMP5, anti-Gephrin, and anti-GABATRAP) and antibodies recently identified against cell surface and synaptic proteins (anti-NMDAR, anti-LGI1, and anti-Caspr2)...
September 25, 2018: Reviews in the Neurosciences
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