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https://www.readbyqxmd.com/read/28601286/autoantibody-responses-to-nodal-and-paranodal-antigens-in-chronic-inflammatory-neuropathies
#1
E K Mathey, N Garg, S B Park, T Nguyen, S Baker, N Yuki, C Yiannikas, C S Lin, J M Spies, R Ghaoui, M H Barnett, S Vucic, J D Pollard, M C Kiernan
Autoantibodies to nodal/paranodal proteins have been reported in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). To determine the frequency of anti-paranodal antibodies in our cohort of CIDP patients and to validate the presence anti-nodal antibodies in MMN, sera were screened for IgG against human neurofascin 155, contactin-1, neurofascin 186 and gliomedin using ELISA. In CIDP patients, 7% were anti-NF155 IgG4 positive and 7% were anti-CNTN1 IgG4 positive...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28588433/intragenic-cntnap2-deletions-a-bridge-too-far
#2
REVIEW
Martin Poot
Intragenic deletions of the contactin-associated protein-like 2 gene (CNTNAP2) have been found in patients with Gilles de la Tourette syndrome, intellectual disability (ID), obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, stuttering, and attention deficit hyperactivity disorder. A variety of molecular mechanisms, such as loss of transcription factor binding sites and perturbation of penetrance and expressivity, have been proposed to account for the phenotypic variability resulting from CNTNAP2 mutations...
May 2017: Molecular Syndromology
https://www.readbyqxmd.com/read/28575198/autoantibodies-to-nodal-isoforms-of-neurofascin-in-chronic-inflammatory-demyelinating-polyneuropathy
#3
Emilien Delmont, Constance Manso, Luis Querol, Andrea Cortese, Angela Berardinelli, Alessandro Lozza, Maya Belghazi, Pauline Malissart, Pierre Labauge, Guillaume Taieb, Nobuhiro Yuki, Isabel Illa, Shahram Attarian, Jérôme J Devaux
Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier...
May 28, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28572274/caspr2-autoantibodies-are-raised-during-pregnancy-in-mothers-of-children-with-mental-retardation-and-disorders-of-psychological-development-but-not-autism
#4
Ester Coutinho, Leslie Jacobson, Marianne Giørtz Pedersen, Michael Eriksen Benros, Bent Nørgaard-Pedersen, Preben Bo Mortensen, Paul J Harrison, Angela Vincent
BACKGROUND, METHODS AND OBJECTIVES: Maternal autoantibodies to neuronal proteins may be one cause of neurodevelopmental disorders. This exploratory study used the Danish archived midgestational sera and their nationwide registers to search for antibodies to the N-methyl-D-aspartate receptor (NMDAR) and contactin-associated protein-like 2 (CASPR2) in maternal sera, and to relate them to subsequent psychiatric diagnoses in the woman or her child. RESULTS: In a sample of 192 women, there was no association between antibody status and subsequent psychosis in the mothers...
June 1, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28565865/alterations-of-caspr2-and-nav1-6-on-myelinated-axon-damage-in-a-rat-model-of-chronic-cerebral-hypoperfusion
#5
Weihua Liang, Weiwei Zhang, Shifu Zhao, Hua Liang, Jinli Zhang, Luyan Wang
Myelinated axons require the correct localization of key proteins that are essential for nerve conduction and cognitive function. Little is known regarding the altered expression of contactin-associated protein 2 (Caspr2) at the juxtaparanodal regions and Nav1.6 at the node of Ranvier in response to chronic cerebral hypoperfusion (CCH). The aim of the present study was to examine the alterations in the key protein of myelinated axons and the potential mechanisms that may follow CCH. We established a rat model of CCH by controllable partial narrowing of bilateral common carotid arteries...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28544133/autoimmune-encephalitis-associated-with-voltage-gated-potassium-channels-complex-and-leucine-rich-glioma-inactivated-1-antibodies-a-national-cohort-study
#6
M Celicanin, M Blaabjerg, C Maersk-Moller, S Beniczky, L Marner, C Thomsen, F W Bach, D Kondziella, H Andersen, F Somnier, Z Illes, L H Pinborg
BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment...
May 25, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28507505/protein-protein-interaction-among-the-foxp-family-members-and-their-regulation-of-two-target-genes-vldlr-and-cntnap2-in-the-zebra-finch-song-system
#7
Ezequiel Mendoza, Constance Scharff
The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28461116/anti-neuronal-anti-bodies-in-patients-with-early-psychosis
#8
O Mantere, M Saarela, T Kieseppä, T Raij, T Mäntylä, M Lindgren, E Rikandi, W Stoecker, B Teegen, J Suvisaari
It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2)...
April 28, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28448609/six-autoantibodies-associated-with-autoimmune-encephalitis-are-not-detectable-in-the-cerebrospinal-fluid-of-suicide-attempters
#9
Johan Fernström, Åsa Westrin, Cécile Grudet, Lil Träskman-Bendz, Lena Brundin, Daniel Lindqvist
Previous findings suggest a link between neuroinflammatory processes and suicidality. Despite several lines of evidence supporting this link, including increased pro-inflammatory markers in blood-, cerebrospinal fluid (CSF)- and in post-mortem brain samples from suicidal individuals, the underlying mechanisms remain poorly understood. In this pilot study, we explored the possibility that autoimmune encephalopathies might be found among suicide attempters. We analysed the presence of six different autoantibodies (N-methyl-D-aspartate receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid receptor, the γ-amino-butyric acid B-receptor, the leucine-rich, glioma-inactivated 1, the contactin-associated protein-like 2, and the dipeptidyl-peptidase-like protein-6), all previously associated with psychopathology, in CSF samples from 29 unmedicated suicide attempters...
2017: PloS One
https://www.readbyqxmd.com/read/28432047/delayed-lgi1-seropositivity-in-voltage-gated-potassium-channel-vgkc-complex-antibody-limbic-encephalitis
#10
Michael Sweeney, Jonathan Galli, Scott McNally, Anne Tebo, Thomas Haven, Perla Thulin, Stacey L Clardy
We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation...
April 20, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28413940/elevated-mrna-expression-of-caspr3-in-patients-with-schizophrenia
#11
Mitsuo Okita, Yuta Yoshino, Jun-Ichi Iga, Shu-Ichi Ueno
BACKGROUND: Recently, it was reported that antipsychotic treatment reverted Contactin Associated Protein-Like 3 (CASPR3, same as CNTNAP3) mRNA expressions in leukocytes of schizophrenia (SCZ) subjects to the same levels as healthy controls. CASPR3 was expressed in various regions of the mice brain (cortex, frontal lobes, corpus callosum, hippocampus, etc.). Thus, this study evaluated CASPR3 mRNA expression in SCZ subjects to find a new clue of schizophrenia pathogenesis. METHODS: One hundred SCZ subjects and 100 age-matched controls were compared...
May 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/28370195/axonal-domain-disorganization-in-caspr1-and-caspr2-mutant-myelinated-axons-affects-neuromuscular-junction-integrity-leading-to-muscle-atrophy
#12
Julia Saifetiarova, Xi Liu, Anna M Taylor, Jie Li, Manzoor A Bhat
Bidirectional interactions between neurons and myelinating glial cells result in formation of axonal domains along myelinated fibers. Loss of axonal domains leads to detrimental consequences on nerve structure and function, resulting in reduced conductive properties and the diminished ability to reliably transmit signals to the targets they innervate. Thus, impairment of peripheral myelinated axons that project to the surface of muscle fibers and form neuromuscular junction (NMJ) synapses leads to muscle dysfunction...
July 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28364455/cntnap2-knockout-rats-and-mice-exhibit-epileptiform-activity-and-abnormal-sleep-wake-physiology
#13
Alexia M Thomas, Michael D Schwartz, Michael D Saxe, Thomas S Kilduff
Study Objectives: Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD). Methods: Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity...
January 1, 2017: Sleep
https://www.readbyqxmd.com/read/28360810/brain-infiltration-of-immune-cells-in-caspr2-antibody-associated-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#14
Gökçen Ünverengil, Ebru Nur Vanli Yavuz, Erdem Tüzün, Ece Erdağ, Sevil Kabadayi, Bilge Bilgiç, Betül Baykan
INTRODUCTION: Antibodies directed against neuronal surface antigens have recently been identified in patients with focal temporal lobe epilepsy (TLE) of unknown cause and mesial TLE with hippocampal sclerosis (MTLE-HS), thereby emphasizing the role of autoimmunity in TLE. Antibodies to contactin-associated protein-like 2 (CASPR2) are prevalent in MTLE-HS patients. We aimed to find out whether anti-neuronal autoimmunity might be involved in CASPR2 antibody-related MTLE-HS. METHODS: Surgically resected medial temporal lobe specimens of seropositive and seronegative MTLE-HS patients were examined with hematoxylin and eosin and immunohistochemical staining using specific immune cell markers...
December 2016: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/28346043/structural-abnormalities-in-the-primary-somatosensory-cortex-and-a-normal-behavioral-profile-in-contactin-5-deficient-mice
#15
Kristel T E Kleijer, Denise van Nieuwenhuize, Henk A Spierenburg, Sara Gregorio-Jordan, Martien J H Kas, J Peter H Burbach
Contactin-5 (Cntn5) is an immunoglobulin cell adhesion molecule that is exclusively expressed in the central nervous system. In view of its association with neurodevelopmental disorders, particularly autism spectrum disorder (ASD), this study focused on Cntn5-positive areas in the forebrain and aimed to explore the morphological and behavioral phenotypes of the Cntn5 null mutant (Cntn5(-/-)) mouse in relation to these areas and ASD symptomatology. A newly generated antibody enabled us to elaborately describe the spatial expression pattern of Cntn5 in P7 wild type (Cntn5(+/+)) mice...
March 27, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28341002/seroprevalence-survey-of-selective-anti-neuronal-autoantibodies-in-patients-with-first-episode-schizophrenia-and-chronic-schizophrenia
#16
Chia-Hsiang Chen, Min-Chih Cheng, Chih-Min Liu, Chen-Chung Liu, Ko-Huan Lin, Hai-Gwo Hwu
Autoimmune encephalopathy caused by autoantibodies against neuronal cell-surface proteins in the brain is a newly discovered disease category associated with psychiatric disorders. Correct diagnosis of this condition relies on the detection of specific autoantibodies in the blood or cerebral spinal fluid in addition to the clinical presentations. The study aimed to understand the seroprevalence of selective anti-neuronal autoantibodies in our patients with schizophrenia. First, we screened for six anti-neuronal autoantibodies in an archived blood sample collected from patients with the first-episode schizophrenia...
March 21, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28321435/amyloid-precursor-protein-family-as-unconventional-go-coupled-receptors-and-the-control-of-neuronal-motility
#17
REVIEW
Jenna M Ramaker, Philip F Copenhaver
Cleavage of the Amyloid Precursor Protein (APP) generates amyloid peptides that accumulate in Alzheimer Disease (AD), but APP is also upregulated by developing and injured neurons, suggesting that it regulates neuronal motility. APP can also function as a G protein-coupled receptor that signals via the heterotrimeric G protein Gαo, but evidence for APP-Gαo signaling in vivo has been lacking. Using Manduca as a model system, we showed that insect APP (APPL) regulates neuronal migration in a Gαo-dependent manner...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28318976/assembly-of-cns-nodes-of-ranvier-in-myelinated-nerves-is-promoted-by-the-axon-cytoskeleton
#18
Veronica Brivio, Catherine Faivre-Sarrailh, Elior Peles, Diane L Sherman, Peter J Brophy
Nodes of Ranvier in the axons of myelinated neurons are exemplars of the specialized cell surface domains typical of polarized cells. They are rich in voltage-gated sodium channels (Nav) and thus underpin rapid nerve impulse conduction in the vertebrate nervous system [1]. Although nodal proteins cluster in response to myelination, how myelin-forming glia influence nodal assembly is poorly understood. An axoglial adhesion complex comprising glial Neurofascin155 and axonal Caspr/Contactin flanks mature nodes [2]...
April 3, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28284582/the-association-of-cntnap2-rs7794745-gene-polymorphism-and-autism-in-iranian-population
#19
Sahar Zare, Farhad Mashayekhi, Elham Bidabadi
Autism is a heterogeneous and multifactorial disease that results from the interaction between genetic vulnerability and environmental factors. Several studies showed that many of genes that play role in autism are component of signaling networks that regulate growth and synaptic plasticity, play an important role in the etiology of autism. Contactin associated-like 2 (CNTNAP2) gene is a member of the superfamily of synaptic adhesion proteins and encodes a scaffold protein called CASPR2 that is involved in the interaction of neuron-glia and clusters K(+) channels in myelinated axons...
May 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28284337/autoimmune-limbic-encephalitis-with-anti-contactin-associated-protein-like-2-antibody-secondary-to-pembrolizumab-therapy
#20
Michael P Brown, Pravin Hissaria, Amy Hc Hsieh, Christopher Kneebone, Wilson Vallat
Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma.
April 15, 2017: Journal of Neuroimmunology
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