Breast Cancer Specificities of Patients With Anti-Ri Paraneoplastic Neurologic Syndromes.

Background And Objectives: Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).

Identification of Predictors of Shift Work Adaptation and Its Association With Immune, Hormonal and Metabolite Biomarkers.

We explored predictors of shift work adaptation and how it relates to disease risk biomarker levels. These analyses included 38 male, rotating shift workers, sampled twice at the end of a 3-week night shift and a 3-week day shift rotation. Participants collected all 24-h urine voids, wore activity sensors, and responded to questionnaires during each shift.

HLA and KIR genetic association and NK cells in anti-NMDAR encephalitis.

Introduction: Genetic predisposition to autoimmune encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDAR) is poorly understood. Given the diversity of associated environmental factors (tumors, infections), we hypothesized that human leukocyte antigen () and killer-cell immunoglobulin-like receptors (), two extremely polymorphic gene complexes key to the immune system, might be relevant for the genetic predisposition to anti-NMDAR encephalitis. Notably, KIR are chiefly expressed by Natural Killer (NK) cells, recognize distinct HLA class I allotypes and play a major role in anti-tumor and anti-infection responses.

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABAR Antibodies.

Background And Objectives: While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABAR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied.

Methods: Patients with GABAR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples.

Anti-AGO1 Antibodies Identify a Subset of Autoimmune Sensory Neuronopathy.

Background And Objectives: Autoantibodies (Abs) improve diagnosis and treatment decisions of idiopathic neurologic disorders. Recently, we identified Abs against Argonaute (AGO) proteins as potential autoimmunity biomarkers in neurologic disorders. In this study, we aim to reveal (1) the frequency of AGO1 Abs in sensory neuronopathy (SNN), (2) titers and IgG subclasses, and (3) their clinical pattern including response to treatment.

A cerebellar degeneration-related protein 2-like cell-based assay for anti-Yo detection in patients with paraneoplastic cerebellar degeneration.

Background And Purpose: Commercially available tests for Yo antibody detection have low specificity for paraneoplastic cerebellar degeneration (PCD) because these assays use cerebellar degeneration-related protein 2 (CDR2) as the antigen, not CDR2-like (CDR2L). We aimed to test the hypothesis that use of a CDR2L cell-based assay (CBA), as an additional screening technique, would increase the accuracy of Yo-PCD diagnosis.

Methods: An in-house CBA to test for anti-CDR2L antibodies was developed and used to screen sera from 48 patients with confirmed anti-Yo-associated PCD.

Day-night and seasonal variation of human gene expression across tissues.

Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. Overall, most variation across tissues during day-night and among seasons was unique to each cycle.

Argonaute Autoantibodies as Biomarkers in Autoimmune Neurologic Diseases.

Objective: To identify and characterize autoantibodies (Abs) as novel biomarkers for an autoimmune context in patients with central and peripheral neurologic diseases.

Methods: Two distinct approaches (immunoprecipitation/mass spectrometry-based proteomics and protein microarrays) and patients' sera and CSF were used. The specificity of the identified target was confirmed by cell-based assay (CBA) in 856 control samples.

Day-night and seasonal variation of human gene expression across tissues.

Circadian and circannual cycles trigger physiological changes whose reflection on human transcriptomes remains largely uncharted. We used the time and season of death of 932 individuals from GTEx to jointly investigate transcriptomic changes associated with those cycles across multiple tissues. Overall, most variation across tissues during day-night and among seasons was unique to each cycle.

Mild Encephalitis/Encephalopathy with reversible splenial lesion syndrome: An unusual presentation of anti-GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a rare recently defined antibody-mediated encephalitis. Meningo-encephalomyelitis presentation is frequent with lymphocytic pleiocytosis in the cerebro-spinal fluid and brain MRI classically demonstrates in 50% of cases, a linear perivascular enhancement extending radially from the ventricles. Here, we describe 2 cases of pediatric autoimmune GFAP astrocytopathy with limbic encephalitis presentation and peculiar MRI characteristics: one with normal MRI and the second suggestive of Mild Encephalitis/Encephalopathy with reversible splenial lesion syndrome (MERS).

Stroke-Like Presentation of Paraneoplastic Cerebellar Degeneration: a Single-Center Experience and Review of the Literature.

Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017.

Immunopathological characterization of ovarian teratomas associated with anti-N-methyl-D-aspartate receptor encephalitis.

Encephalitis with anti-NMDAR antibodies (NMDAR-E) is a severe autoimmune neurological disorder, defined by a clinical presentation of encephalitis and the presence of IgG targeting the GluN1 subunit of NMDA receptors in the CSF. An underlying ovarian teratoma is commonly associated with this autoimmune disease suggesting a role of the tumor in immunopathogenesis. In this study, we characterized the salient histopathological features of 27 ovarian teratomas associated with NMDAR-E (3 immature and 24 mature teratomas) and 40 controls without associated encephalitis.

EEG analysis in anti-NMDA receptor encephalitis: Description of typical patterns.

Objective: To describe different electroencephalogram (EEG) patterns and epileptic features in patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE), their timeline in the course of the disease, their correlation with clinical data and outcome.

Methods: We retrospectively analyzed EEG recordings between November 2007 and June 2016 in 24 consecutive patients.

Results: Three EEG patterns were described: Excessive Beta Activity range 14-20 Hz (EBA) in 71% of patients, Extreme Delta Brush (EDB) in 58% and Generalized Rhythmic Delta Activity (GRDA) in 50%.

Isolated seizures are a common early feature of paraneoplastic anti-GABA receptor encephalitis.

Objective: To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABA receptor antibodies (GABAR-Abs).

Methods: Retrospective clinical study of CSF-confirmed cases of GABAR-Abs encephalitis.

Results: We identified 22 patients (4 female) with GABAR-Abs, with a median age of 64 years (range 55-85).

Structural mapping of hot spots within human CASPR2 discoidin domain for autoantibody recognition.

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.

Contactin-associated protein-like 2, a protein of the neurexin family involved in several human diseases.

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.

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies.

Background: Paraneoplastic neurological syndromes are rare conditions where an autoimmune reaction against the nervous system appears in patients suffering from a tumour, but not linked to the spreading of the tumour. A break in the immune tolerance is thought to be the trigger.

Methods: The transcriptomic profile of 12 ovarian tumours (OT) from patients suffering from paraneoplastic cerebellar degeneration (PCD) linked to anti-Yo antibodies (anti-Yo PCD OT) was compared with 733 ovarian tumours (OT control) from different public databases using linear model analysis.