Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls.

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.

HLA-DR3 ~ DQ2 associates with sensory neuropathy in paraneoplastic neurological syndromes with Hu antibodies.

Objectives: To investigate the association between human leukocyte antigen (HLA) and paraneoplastic neurological syndromes (PNS) with Hu antibodies, and potential specificities according to clinical presentation and cancer status.

Methods: HLA genotypes at four-digit resolution were imputed from available genome-wide association data. Allele carrier frequencies were compared between patients (whole cohort, n = 100, and according to clinical presentation and cancer status) and matched healthy controls (n = 508) using logistic regression controlled by the three main principal components.

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.

Different Genetic Signatures of Small-Cell Lung Cancer Characterize Anti-GABA R and Anti-Hu Paraneoplastic Neurological Syndromes.

Objective: Small-cell lung cancer (SCLC) is the malignancy most frequently associated with paraneoplastic neurological syndromes (PNS) and can trigger different antibody responses against intracellular (Hu) or neuronal surface (GABA R) antigens. Our aim was to clarify whether the genomic and transcriptomic features of SCLC are different in patients with anti-GABA R or anti-Hu PNS compared with SCLC without PNS.

Methods: A total of 76 SCLC tumor samples were collected: 34 anti-Hu, 14 anti-GABA R, and 28 SCLC without PNS.

SOX1 antibody-related paraneoplastic neurological syndromes: clinical correlates and assessment of laboratory diagnostic techniques.

Objective: To describe the clinical associations of SOX1 antibodies (SOX1-Abs), determine the accuracy of various detection techniques, and propose laboratory criteria to identify definite paraneoplastic neurological syndromes (PNS) associated with SOX1-Abs.

Methods: Single-center, retrospective study of patients referred to the French Reference Center between 2009 and 2019 for confirmation of SOX1-Ab positivity, without concurrent neural antibodies. Patients were classified according to the updated diagnostic PNS criteria; biological samples were systematically retested with three distinct techniques (line blot, cell-based assay, indirect immunofluorescence).

Early-Stage Contactin-Associated Protein-like 2 Limbic Encephalitis: Clues for Diagnosis.

Background And Objectives: Previous studies suggested that autoimmune limbic encephalitis with antibodies against contactin-associated protein-like 2 (CASPR2-encephalitis) is clinically heterogeneous and progresses slowly, preventing its early recognition. We aimed to describe the onset and progression of CASPR2-encephalitis and to assess long-term outcomes.

Methods: We retrospectively analyzed the medical records of all patients whose CSF tested positive for anti-CASPR2 antibodies in our center between 2006 and 2020.

Cerebellar Ataxia With Anti-DNER Antibodies: Outcomes and Immunologic Features.

Background And Objectives: There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor-related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies.

Methods: Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively.

Immunopathogenesis and proposed clinical score for identifying Kelch-like protein-11 encephalitis.

In this study, we report the clinical features of Kelch-like protein 11 antibody-associated paraneoplastic neurological syndrome, design and validate a clinical score to facilitate the identification of patients that should be tested for Kelch-like protein 11 antibodies, and examine in detail the nature of the immune response in both the brain and the tumour samples for a better characterization of the immunopathogenesis of this condition. The presence of Kelch-like protein 11 antibodies was retrospectively assessed in patients referred to the French Reference Center for paraneoplastic neurological syndrome and autoimmune encephalitis with (i) antibody-negative paraneoplastic neurological syndrome [limbic encephalitis ( = 105), cerebellar degeneration ( = 33)] and (ii) antibody-positive paraneoplastic neurological syndrome [Ma2-Ab encephalitis ( = 34), antibodies targeting N-methyl-D-aspartate receptor encephalitis with teratoma ( = 49)]. Additionally, since 1 January 2020, patients were prospectively screened for Kelch-like protein 11 antibodies as new usual clinical practice.

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.

Clinical and Prognostic Value of Immunogenetic Characteristics in Anti-LGI1 Encephalitis.

Objective: Antibodies against leucine-rich glioma-inactivated 1 (LGI1-Abs) characterize a limbic encephalitis (LE) strongly associated with HLA-DRB1*07:01, although some patients lack LGI1-Abs in CSF or do not carry this allele. Whether they represent a different subtype of disease or have different prognoses is unclear.

Methods: Retrospective analysis of clinical features, IgG isotypes, and outcome according to LGI1-Ab CSF positivity and DRB1*07:01 in a cohort of anti-LGI1 LE patients.

Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis.

Limbic encephalitis with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leucocyte antigen and CSF proteomic profiles. Patients with anti-AK5 limbic encephalitis were mostly male (20/26, 76.

Clinical features, prognostic factors, and antibody effects in anti-mGluR1 encephalitis.

Objective: To clinically characterize patients with anti-metabotropic glutamate receptor (mGluR) 1 encephalitis, to identify prognostic factors, and to study the immunoglobulin G (IgG) subclasses and effects of antibodies on neuronal mGluR1 clusters.

Methods: Clinical information on new and previously reported patients was reviewed. Antibodies to mGluR1 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays, and their effects on mGluR1 clusters were studied on rat hippocampal neurons.

Anti-CASPR2 clinical phenotypes correlate with HLA and immunological features.

Objective: Antibodies against contactin-associated protein-like 2 (CASPR2-Abs) have been described in acquired neuromyotonia, limbic encephalitis (LE) and Morvan syndrome (MoS). However, it is unknown whether these constitute one sole spectrum of diseases with the same immunopathogenesis or three distinct entities with different mechanisms.

Methods: A cluster analysis of neurological symptoms was performed in a retrospective cohort of 56 CASPR2-Abs patients.

Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors.

Objective: To report the induction of anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) in 6 patients after treatment with immune checkpoint inhibitors (ICIs). We also analyzed (1) patient clinical features compared with a cohort of 44 patients who developed Ma2-PNS without receiving ICI treatment and (2) the frequency of neuronal antibody detection before and after ICI implementation.

Methods: Retrospective nationwide study of all patients with Ma2-PNS developed during ICI treatment between 2017 and 2018.

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).