Antineuronal Antibodies In Patients Research Articles

Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 – A National Cohort Study

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated.

Sera anti-neuronal antibodies in patients with irritable bowel syndrome and their correlations with clinical profiles.

Immune factors were involved in the pathophysiology of irritable bowel syndrome (IBS). The aim of the study was to test anti-neuronal antibodies in sera of IBS patients and demonstrate their correlations with IBS profiles and psychological disorders. Patients with IBS met Rome III criteria and excluded organic diseases were enrolled. Controls included healthy subjects (HS), slow transit functional constipation, autoimmune diseases, and so on. Indirect immunofluorescence with monkey cerebellum and small intestine as substrates was used to detect anti-neuronal antibodies including anti-cerebral neuronal antibodies (ACNA) and anti-enteric neuronal antibodies (AENA). A total of 293 IBS patients, 100 HS and 153 disease controls were included in this study. The ACNA positive rate of IBS patients was significantly higher than HS (14% vs. 6%, p = 0.033). The positive rate of ACNA was significantly lower than AENA (14.0% vs. 76.8%, p = 0.028) in IBS patients. The prevalence of headache and sleeping disorder were higher in ACNA-positive IBS patients than ACNA-negative IBS patients (61% vs. 42.9%, p = 0.03; 75.6% vs. 57.1%, p = 0.03, respectively). Among IBS patients, ACNA and AENA were both negative in 21.8% patients, ACNA negative and AENA positive in 64.2% patients, and ACNA and AENA were both positive in 12.6% patients. There were no significant differences of intestinal symptoms among the three groups, while the prevalence of headache (64.9% vs. 37.5% and 44.7%, p = 0.03) and sleeping disorder (78.4% vs. 50.0% and 59.6%, p = 0.02) were higher in patients with both ACNA and AENA positive than patients with both ACNA and AENA negative, patients with ACNA negative and AENA positive. There were no significant differences of the prevalence of depression and anxiety, HAMD, and HAMA scores among the three groups. Anti-neuronal antibodies in sera of IBS patients were mainly targeted to enteric neurons and in a small part to cerebral neurons. ACNA were closely related to headache and sleeping disorder but unrelated to intestinal symptoms, depression, or anxiety of IBS patients.

Autoimmune Mechanisms in Focal Epilepsy of Unknown Cause

ABSTRACT The manifestation of immunological findings in diverse disorders presenting with seizures points to autoimmunity and inflammation in the etiology of epilepsy. Typical examples of autoimmunity-associated epilepsy are autoimmune encephalitis, Rasmussen encephalitis, and glutamic acid decarboxylase (GAD) antibody-positive temporal lobe epilepsy (TLE). The last entity is a typical example of antibody-positive focal epilepsy of unknown cause (FEUC). One of the most prominent findings emphasizing the coexistence of epilepsy and autoimmunity is the detection of anti-neuronal antibodies in patients manifesting with seizures. Emergence of antibody-producing plasma cells in the early course of GAD-antibody-positive TLE and induction of seizures in rodents upon intracerebral administration of N-methyl-D-aspartate receptor antibodies indicate that anti-neuronal antibodies may play a causal (rather than bystander) role in the induction of seizures. By contrast, innate immunity of the central nervous system (CNS) and infiltrating cytotoxic T-cells appear to participate in Rasmussen encephalitis and autoimmune encephalitis with antibodies to intracellular antigens. In addition, repetitive seizures may activate glial cells through the release of damage-associate molecular pattern mediators and activation of toll-like receptors, which in turn leads to disrupted blood–brain barrier and increased cerebral infiltration of peripheral blood immune cells. In conclusion, complex interactions of humoral and cellular immunity in the CNS appear to cause or at least contribute to seizure induction in FEUC. The nature of these interactions has recently started to be understood. Investigation of these mechanisms is substantial for the discovery of new treatment strategies and biomarkers in epilepsy.

Coexistence of multiple anti-neuronal antibodies in autoimmune encephalitis in China: A multi-center study.

BackgroundGiven that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE.MethodsWe conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China.ResultsAmong the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications.ConclusionThe coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.

Anti-N-Methyl-d-Aspartate Receptor Antibody Testing in First-Episode Psychosis: Universal or Targeted Testing.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder that typically presents with rapid development of neuropsychiatric symptoms. As a potentially reversible cause of psychosis, there have been calls internationally for routine serological screening for anti-NMDAR antibodies in patients presenting with first-episode psychosis (FEP). Increased serological testing has, however, exposed several limitations of universal screening and rekindled debate as to which patients should be tested. Screening criteria have been proposed for high-risk clinical features in FEP in which antineuronal antibody testing is indicated. The authors present a clinical vignette and a service audit as well as discuss the limitations of universal screening advocating instead for targeted testing for antineuronal antibodies in patients diagnosed as having FEP.

Anti-Neuronal Autoantibodies (Cell Surface and Onconeural) and Their Association With Natural Autoantibodies in Synthetic Cannabinoid-Induced Psychosis.

Patients suffering from encephalitis may present psychiatric symptoms; however, the clinical relevance of anti-neuronal antibodies in patients experiencing a psychotic episode without encephalitis is still unclear. In this study, we examined the presence of anti-neuronal cell surface autoantibodies and onconeural autoantibodies in serum samples of 22 synthetic cannabinoid users presenting with psychosis. We found only two positive cases; however, seven patients had borderline results. Nonetheless, we found no significant correlation between anti-neuronal autoantibodies and the intensity of psychosis indicated by the Positive and Negative Syndrome Scale (PANSS) scores. The length of drug use and the combination of other drugs with synthetic cannabinoids have no significant effect on anti-neuronal autoantibody positivity. Nonetheless, the ratio of anti-citrate synthase (anti-CS) IgM and IgG natural autoantibodies was significantly lower (p = 0.036) in the anti-neuronal autoantibody-positive/borderline samples, than in the negative group. Interestingly, anti-CS IgM/IgG showed a significant negative correlation with PANSS-positive score (p = 0.04, r = −0.464). Our results demonstrated that anti-neuronal autoantibody positivity occurs in synthetic cannabinoid users, and the alteration of anti-CS IgM/IgG natural autoantibody levels points to immunological dysfunctions in these cases.

Common paraneoplastic neurological syndromes in Pakistan: Clinical and immunological aspects

To determine the frequency and clinical features associated with anti-neuronal antibodies in patients suspected of paraneoplastic neurological syndromes and autoimmune encephalitis in a tertiary care hospital in Islamabad, Pakistan.

KNOCK KNOCK, HU'S THERE? POSITIVE ANTI-HU ANTIBODY IN EXTRAPULMONARY SMALL CELL CARCINOMA OF LYMPH NODE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: To date, small cell carcinoma (SCC) has been primarily recognized as a pulmonary malignancy and research has been skewed towards this area. Extrapulmonary SCC is rare, accounting for 2.5% of SCC, out of which lymph node SCC are far and few between. CASE PRESENTATION: A 59-year-old gentleman was initially admitted to neurology for sensory neuropathy and weight loss. He was referred to the respiratory medicine team after imaging revealed subcarinal and left hilar lymphadenopathy. He is a chronic smoker and there was a concern for malignancy. Initial endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) using 22 gauge needle showed lymphoid yield. Serum paraneoplastic panel (Hu, Yo, Ri, CV2, Amphiphysin, PNMA2/Ta, recoverin, SOX1, titin, zic4, GAD65, Tr(DNER)) was performed as part of the diagnostic work up. Anti-Hu antibody was 1:101 (strongly positive); reference titer 1:<10. Fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan revealed FDG avid subcarinal (SUVmax:11.1) and left hilar (SUVmax:13.2) nodes. In view of the anti-Hu antibody results and FDG-PET-CT findings, a repeat EBUS-TBNA using 19 gauge needle was performed and histology confirmed SCC. DISCUSSION: Paraneoplastic syndrome was first described by M. Auché in 1890 and is known to affect up to 8% of patients with cancer; most notably small cell lung cancer. Anti-Hu is an onconeural antibody first discovered by F. Grouse in 1985. Its moniker is type I anti-neuronal nuclear antibody (ANNA-1) and has been a signpost for paraneoplastic sensory neuropathy or encephalomyelitis. (Positive anti-Hu antibody titers have a reported specificity of 99% and sensitivity of 82%). It is recognized as a distinct clinical disease, “anti-Hu syndrome”, with characteristic clinical picture and imaging findings. A Dutch study in 2002 found that 85% of patients with positive anti-Hu antibody also have a tumor. Of note, anti-Hu antibodies can also be positive in antecedent inflammatory diseases like systemic lupus erythematosus or Sjogren’s syndrome which can confound the diagnosis. Thus, positive anti-Hu antibody levels should prompt further evaluation and follow up even in absence of concurrent malignancy. Early diagnosis of lymph node SCC has prognostic implications when compared to pulmonary and extrapulmonary SCC, thus making the distinction necessary. CONCLUSIONS: This study highlights the diagnostic implications of an abnormal paraneoplastic panel, emphasizing the role of anti-Hu antibody in its specificity for SCC. The presence of FDG avid thoracic lymph nodes with elevated anti-Hu antibody titers warrants a repeat biopsy. It is imperative for clinicians to identify occult neoplasms in the setting of paraneoplastic syndromes. Reference #1: Koike H, Sobue G. Paraneoplastic neuropathy. Handb Clin Neurol. 2013;115:713-26. Reference #2: Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985 Apr;35(4):538–43. Sehgal IS, Kaur H, Dhooria S, et al. Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases. World J Clin Oncol. 2016;7(3):308-20. Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G, Delattre JY. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(6):1138-1148. Senties-Madrid H, Vega-Boada F. Paraneoplastic syndromes associated with anti-Hu antibodies. Isr Med Assoc J. 2001 Feb;3(2):94-103. Reference #3: Benyahia B, Amoura Z, Rousseau A, Le Clanche C, Carpentier A, Piette JC, Delattre JY. Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases. J Neurooncol. 2003 May;62(3):349-51. Sillevis Smitt P, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H, Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 2002 Jun;249(6):745-53. Kim KO, Lee HY, Chun SH, et al. Clinical overview of extrapulmonary small cell carcinoma. J Korean Med Sci. 2006;21(5):833-7. Kannoth S. Paraneoplastic neurologic syndrome: A practical approach. Ann Indian Acad Neurol. 2012;15(1):6-12. DISCLOSURES: No relevant relationships by John Abisheganaden, source=Web Response No relevant relationships by Caroline Choong, source=Web Response No relevant relationships by Sharlene Ho, source=Web Response No relevant relationships by Chuen Peng Lee, source=Web Response No relevant relationships by Ziqin Ng, source=Web Response No relevant relationships by Ser Hon Puah, source=Web Response No relevant relationships by HUIJIA WANG, source=Web Response No relevant relationships by Kim Hoong Yap, source=Web Response

The significance of anti-neuronal antibodies for acute psychiatric disorders: a retrospective case\u2013controlled study

BackgroundThe clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls.ResultsPatients who were serum-positive to N-methyl d-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls.ConclusionIn this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.

Autoantibody-Mediated Encephalitis.

Acute and subacute disturbances of wakefulness and cognitive function are common neurological manifestations in the hospital and in outpatient care. An important element of the differential diagnosis was described only a few years ago: autoimmune encephalitis, a condition whose diagnosis and treatment pose an interdisciplinary challenge. This review is based on pertinent publications from the years 2005-2017 that were retrieved by a selective search in PubMed, and on the authors' personal experience and case reports. The incidence of autoimmune encephalitis in Germany is estimated at 8-15 cases per million persons per year. In some patients with psychotic manifestations or impaired consciousness of acute or subacute onset, an autoimmune patho - genesis can be demonstrated by the laboratory detection of autoantibodies against neuronal target antigens (e.g., glutamate receptors). Testing of this type should be performed in patients with inflammatory changes in the cerebrospinal fluid or on magnetic resonance imaging (MRI), or those who have had an otherwise unexplained first epileptic seizure or status epilepticus. The cumulative sensitivity of testing for all potentially causative antineuronal antibodies in patients with clinically defined autoimmune encephalitis is estimated at 60-80 %. Figures on cumulative specificity are currently unavailable. The detection of antineuronal antibodies in patients with the corresponding appropriate symptoms implies the diagnosis of autoimmune encephalitis. Observational studies have shown that rapidly initiated immunosuppressive treatment improves these patients' outcomes. Further studies are needed to determine the positive predictive value of antineuronal antibody detection and to develop further treatment options under randomized and controlled conditions.

38.4 PREVALENCE OF ANTI-NEURONAL ANTIBODIES IN PATIENTS ADMITTED WITH FIRST EPISODE OF PSYCHOSIS AND THEIR CLINICAL OUTCOMES

BackgroundAnti-neuronal antibodies are associated with psychosis although their clinical significance in first episode of psychosis (FEP) is undetermined. This study examined the prevalence of anti-neuronal antibodies in patients admitted to hospital for treatment of their first episode of psychosis and described clinical presentations and treatment outcomes of those who were antibody positive.MethodsBetween July 2013 and May 2015, all consenting patients aged between 12 and 50 admitted for their first episode of psychosis to three mental health hospitals in Queensland, Australia, were tested for anti-neuronal antibodies in serum. Antibody positive patients were referred for neurological and immunological consultation and treatment.ResultsDuring the study, 154 FEP patients were admitted with their first episode of psychosis and 113 consented to participate. Six patients were found to have anti-neuronal antibodies; (anti-NMDAR antibodies [n = 4], VGKC antibody [n = 1], antibody against uncharacterised antigen [n = 1]). Of these, five received immunotherapy, leading to complete resolution of psychosis in four.DiscussionA small, but significant subgroup of patients with first episode psychosis have anti-neuronal antibodies detectable in serum and evidence of central nervous system autoimmune pathology. Early identification of these patients and referral for appropriate treatment is critical to optimise recovery.

High prevalence and functional effects of serum antineuronal antibodies in patients with gastrointestinal disorders.

Antineuronal antibodies can be associated with both gastrointestinal (GI) and brain disorders. For example, antibodies against the potassium channel subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central nervous system (CNS) and myenteric plexus and cause encephalitis, commonly preceded by severe unspecific GI symptoms. We therefore investigated the prevalence of antineuronal antibodies indicative of treatable autoimmune CNS etiologies in GI patients. Serum samples of 107 patients (Crohn's disease n=42, ulcerative colitis n=16, irritable bowel syndrome n=13, others n=36) and 44 healthy controls were screened for anti-DPPX and further antineuronal antibodies using immunofluorescence on rat brain and intestine and cell-based assays. Functional effects of high-titer reactive sera were assessed in organ bath and Ussing chamber experiments and compared to non-reactive patient sera. Twenty-one of 107 patients (19.6%) had antibodies against the enteric nervous system, and 22 (20.6%) had anti-CNS antibodies, thus significantly exceeding frequencies in healthy controls (4.5% each). Screening on cell-based assays excluded established antienteric antibodies. Antibody-positive sera were not associated with motility effects in organ bath experiments. However, they induced significant, tetrodotoxin (TTX)-insensitive secretion in Ussing chambers compared to antibody-negative sera. Antineuronal antibodies were significantly more frequent in GI patients and associated with functional effects on bowel secretion. Future studies will determine whether such antibodies indicate patients who might benefit from additional antibody-directed therapies. However, well-characterized encephalitis-related autoantibodies such as against DPPX were not detected, underlining their rarity in routine cohorts.

Anti-neuronal anti-bodies in patients with early psychosis

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). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues.

Prevalence of antineuronal antibodies in patients with encephalopathy of unknown etiology: Data from a nationwide registry in Korea

We aimed to evaluate the prevalence of antineuronal antibodies in a nationwide cohort of patients with encephalopathy of unknown etiology. We screened 1699 patients with idiopathic encephalopathy who were referred from 70 hospitals across Korea for autoimmune synaptic and classic paraneoplastic antibodies. Those with cerebellar degeneration, sensory polyneuropathy or other paraneoplastic syndromes without encephalopathy were not included in this study. One-hundred and four patients (6.12%) had antibody-associated autoimmune encephalopathy. Autoimmune synaptic antibodies were identified in 89 patients (5.24%) and classic paraneoplastic antibodies were identified in 16 patients (0.94%). The patients with antibody-associated autoimmune encephalopathy comprised a small but significant portion of the total number of patients with encephalopathy of unknown cause.

Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease.

Objective:To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD).Methods:The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998–2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in CSF obtained postmortem by immunohistochemistry on fresh frozen rat brain sections, by Luminex assay for the presence of well-characterized onconeural antibodies, and by cell-based assays for antibodies against NMDAR, GABABR1/2, GABAAR GLUR1/2, LGI1, Caspr2, and DPPX.Results:In 203 patients, a diagnosis of definite CJD was made, while in 181 a variety of other conditions were diagnosed, mainly neurodegenerative. In 22 of these 181, the neuropathologist diagnosed autoimmune encephalitis. One patient was excluded because of lack of clinical information. Inflammatory infiltrates were predominantly perivascular and consisted mainly of T cells. The predominant locations were basal ganglia and thalamus (90%) and temporal lobes and hippocampus (81%). In 6 patients (29%), antineuronal antibodies were detected in postmortem CSF, directed against Hu, NMDAR, GABABR1/2, Caspr2, and an unidentified synaptic antigen in 2. The most frequent symptoms were dementia (90%), gait disturbance (86%), cerebellar signs (67%), and neuropsychiatric symptoms (67%). Immunopathologic and clinical findings did not differ between autoantibody-negative patients and patients with antineuronal antibodies.Conclusions:It is important to consider immune-mediated disorders in the differential diagnosis of rapidly progressive neurologic deficits.

Hydrogen peroxide mediated the neurotoxicity of an antibody against plasmalemmal neuronspecific enolase in primary cortical neurons

Neuron-specific enolase (NSE) is not only a glycolytic enzyme in the cytosol, but also localized in the synaptic plasma membrane. The plasmalemmal NSE is one of autoantigen targets in post-streptococcal autoimmune central nervous system disease. Although anti-neuronal antibodies in patients bind to a restricted group of NSE in cerebral cortex, it has not yet been clarified how the anti-NSE antibody have negative impacts on cortical neurons. Here, we found that NSE was also localized at neuronal cell bodies and neuritis on the neuronal cell surface in the primary culture of rat cortical neurons. The anti-NSE antibody induced neuronal cell death in a concentration-dependent manner. The neuronal cell death required a lag time and was not accompanied with caspase-3 activation and chromatin condensation. The anti-NSE antibody elevated a level of intracellular H2O2 prior to neuronal cell death. Catalase protected neurons from the anti-NSE antibody-induced H2O2 generation and cell death. The post-treatment of neurons with catalase after the application of the anti-NSE antibody exhibited neuroprotective effects as well as the co-treatment. The cascade of mitogen-activated protein kinase (MAPK) is one of signal transductions of H2O2. Among MAPK, a c-Jun N-terminal kinase partially contributed to the neurotoxicity of anti-NSE antibody. Thus, the anti-NSE antibody acted at the plasmalemmal NSE, produced H2O2, and caused neuronal cell death via non-apoptotic pathway in the cortical neurons.

Anti-Neuronal Antibodies in Patients with Fragile X Syndrome: Is there a Role of Autoimmunity in Its Pathogenesis?

Background: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and a strong association with autism. Objectives: In this study, the frequency of serum anti-neural antibodies was investigated in FXS patients who did and those who did not manifest autism spectrum disorders (ASD) in comparison to typically developing controls. Methods: The study involved 23 males (mean age, 19.78 ± 6.56 years) who harboured a full mutation in the FMR1 gene. The control group comprised 19 healthy students (mean age 24.63 ± 1.89 years). Serum anti-neuronal antibodies were analyzed using Western blotting. Results: Serum anti-neuronal antibodies were present in 10/23 (43.48%) FXS males. Conclusion: Serum anti-neuronal antibodies were found in a subgroup of FXS patients. Autistic symptoms in FXS may, in part, be caused by auto-immune factors. Further studies in larger patient and control groups are necessary to elucidate the aetiopathogenic role of anti-neuronal antibodies in FXS patients.

Analysis of Antineuronal Antibodies in Patients with Suspected and Pathologically Proven Creutzfeldt-Jakob Disease (P04.218)

Analysis of Antineuronal Antibodies in Patients with Suspected and Pathologically Proven Creutzfeldt-Jakob Disease (P04.218)

Functional effects of anti-neuronal antibodies in patients with encephalitis lethargica and other related disorders associated with streptococcal infection

Functional effects of anti-neuronal antibodies in patients with encephalitis lethargica and other related disorders associated with streptococcal infection

2. Investigation of Novel Antineuronal Antibodies in Patients with Collagen Diseases.

神経障害を伴う膠原病患者において自己免疫異常を背景として出現した抗神経抗体は神経障害に密接な関りをもつ可能性がある．したがって特異的な抗神経抗体を同定することは，その病態解明に重要である．また，時に神経系の日和見感染症や精神疾患との鑑別が問題となるこれら神経症状の，適切な診断と治療効果のメルクマールの確立につながると考えられる．我々はプロテオミクス解析の手法を用いて，神経障害を伴う膠原病に特異的と考えられた新たな抗神経抗体をいくつか同定してきたので報告する．