Autoantibodies in myasthenia gravis.

Autoimmune Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness and autoantibodies. It can be divided by the presence of serum autoantibodies into two major categories where Immunoglobulin G (IgG) against either the acetylcholine receptor (AChR), or muscle specific kinase (MuSK) causes fatigable muscle weakness. The clinical relevance of Low-density lipoprotein-receptor related protein-4 IgG (LRP4) is debated.

Evolution and significance of neuronal surface autoantibodies after Japanese encephalitis.

NMDAR-antibody encephalitis can arise as a post-infectious 'relapse' following HSV encephalitis. We asked whether a similar condition might occur after Japanese Encephalitis (JE). Cell-based assays for antigen-specific antibodies and IgG binding to the surface of live hippocampal neurons were performed on 13 CSFs and 65 sera, many sampled longitudinally, from 34 Vietnamese children with JE.

Case Series of Canine Myasthenia Gravis: A Classification Approach With Consideration of Seronegative Dogs.

Background: Myasthenia gravis (MG) is categorized into several subgroups, including seronegative MG. Seronegative human patients are well documented, but seronegative dogs remain clinically uncharacterized and their prevalence unknown.

Objectives: This study aims to evaluate the clinical presentation, diagnosis, treatment, and outcome of canine MG subgroups.

Permissive central tolerance plus defective peripheral checkpoints license pathogenic memory B cells in CASPR2-antibody encephalitis.

Autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the development of disease-causing B cells and autoantibodies. Convention suggests that such autoreactivities are generated during germinal center reactions. Here, we explore earlier immune checkpoints, focusing on patients with contactin-associated protein-like 2 (CASPR2)-autoantibody encephalitis.

Myasthenia gravis in 2025: five new things and four hopes for the future.

The last 10 years has brought transformative developments in the effective treatment of myasthenia gravis (MG). Beginning with the randomized trial of thymectomy in myasthenia gravis that demonstrated efficacy of thymectomy in nonthymomatous MG, several new treatment approaches have completed successful clinical trials and regulatory launch. These modalities, including B cell depletion, complement inhibition, and blockade of the neonatal Fc receptor, are now in use, offering prospects of sustained remission and neuromuscular protection in what is a long-term disease.

Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing.

Background And Aims: Reliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in-house assays are unknown. We compared testing at four centres.

Permissive central tolerance plus defective peripheral checkpoints licence pathogenic memory B cells in CASPR2-antibody encephalitis.

Autoimmunity affects 10% of the population. Within this umbrella, autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the developmental pathway of disease-causing B cells and autoantibodies. While such autoreactivities are believed to be generated during germinal centre reactions, the roles of earlier immune checkpoints in autoantigen-specific B cell tolerance are poorly understood.

A complex and severe encephalitis associated with four co-existing neuronal cell-surface autoantibodies.

Many forms of autoimmune encephalitis are mediated by neuronal cell-surface directed autoantibodies. The co-occurrence of four neuronal cell-surface antibodies in a single patient is exceptionally rare. We report a patient who had a severe encephalitis associated with antibodies to NMDA, Glycine, GABA and GABA receptors.

Clinical symptoms and psychosocial functioning in patients with schizophrenia spectrum disorders testing seropositive for anti-NMDAR antibodies: a case-control comparison with patients testing negative.

Background: Antibodies against the N-methyl-D-aspartate receptor (NMDAR) have been described in the serum of people with schizophrenia spectrum disorders (schizophrenia). However, the prevalence and clinical relevance of these antibodies in schizophrenia is unclear. This knowledge gap includes the possibility of such antibodies being associated with a distinct clinical profile, which in turn might warrant a distinct treatment approach.

Slowly Expanding Lesions Differentiate Pediatric Multiple Sclerosis from Myelin Oligodendrocyte Glycoprotein Antibody Disease.

Slowly expanding lesions (SELs) in adults with multiple sclerosis (MS) indicate a progressive pathological process. Whether SELs are present in pediatric-onset MS (POMS) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is unknown. We studied 19 children with POMS and 14 with MOGAD (median age 14.

The influence of MOGAD on diagnosis of multiple sclerosis using MRI.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an immune-mediated demyelinating disease that is challenging to differentiate from multiple sclerosis (MS), as the clinical phenotypes overlap, and people with MOGAD can fulfil the current MRI-based diagnostic criteria for MS. In addition, the MOG antibody assays that are an essential component of MOGAD diagnosis are not standardized. Accurate diagnosis of MOGAD is crucial because the treatments and long-term prognosis differ from those for MS.

Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases.

Evolution of methods to detect paraneoplastic antibodies.

An adaptive immune response in less than 1% of people who develop cancer produces antibodies against neuronal proteins. These antibodies can be associated with paraneoplastic syndromes, and their accurate detection should instigate a search for a specific cancer. Over the years, multiple systems, from indirect immunofluorescence to live cell-based assays, have been developed to identify these antibodies.

Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis.

Intrathecal synthesis of central nervous system (CNS)-reactive autoantibodies is observed across patients with autoimmune encephalitis (AE), who show multiple residual neurobehavioral deficits and relapses despite immunotherapies. We leveraged two common forms of AE, mediated by leucine-rich glioma inactivated-1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, as human models to comprehensively reconstruct and profile cerebrospinal fluid (CSF) B cell receptor (BCR) characteristics. We hypothesized that the resultant observations would both inform the observed therapeutic gap and determine the contribution of intrathecal maturation to pathogenic B cell lineages.

Timing of MOG-IgG Testing Is Key to 2023 MOGAD Diagnostic Criteria.

Background And Objectives: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a recently identified autoimmune demyelinating disorder of the CNS affecting both adults and children. Diagnostic criteria for MOGAD have recently been published. We aimed to validate the 2023 MOGAD diagnostic criteria in a real-world cohort of patients with atypical CNS inflammation.

Clinical Usefulness of a Cell-based Assay for Detecting Myelin Oligodendrocyte Glycoprotein Antibodies in Central Nervous System Inflammatory Disorders.

Background: The clinical implications of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Abs) are increasing. Establishing MOG-Ab assays is essential for effectively treating patients with MOG-Abs. We established an in-house cell-based assay (CBA) to detect MOG-Abs to identify correlations with patients' clinical characteristics.

Do Early Relapses Predict the Risk of Long-Term Relapsing Disease in an Adult and Paediatric Cohort with MOGAD?

Objective: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can be monophasic or relapsing, with early relapse being a feature. However, the relevance of early relapse on longer-term relapse risk is unknown. Here, we investigate whether early relapses increase longer-term relapse risk in patients with MOGAD.

Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates.

Background And Objectives: Myasthenia gravis (MG) can in rare cases be an autoimmune phenomenon associated with hematologic malignancies such as chronic lymphocytic leukemia (CLL). It is unclear whether in patients with MG and CLL, the leukemic B cells are the ones directly driving the autoimmune response against neuromuscular endplates.

Methods: We identified patients with acetylcholine receptor antibody-positive (AChR) MG and CLL or monoclonal B-cell lymphocytosis (MBL), a precursor to CLL, and described their clinical features, including treatment responses.

Autoantibody detection by a live cell-based assay in conventionally antibody-tested triple seronegative Myasthenia gravis.

Autoantibody testing is the mainstay in confirming the diagnosis of autoimmune myasthenia gravis (MG). However, in approximately 15% of patients, antibody testing in clinical routine remains negative (seronegative MG). This study aimed at assessing the prevalence of "clustered" AChR- and MuSK- and LRP4- autoantibodies using a live cell-based assay in a large German cohort of seronegative myasthenia gravis (SNMG) patients.