active-immunization-for-inducing-autoimmune-muscle-specific-kinase

Active Immunization for Inducing Autoimmune Muscle-Specific Kinase (MuSK) Myasthenia Gravis in Mice

Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction. While most MG patients produce autoantibodies against the ...

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Autoimmune encephalitis (AE) is a distinct neuro-immunological disorder associated with the production of autoantibodies against neuronal proteins responsible for pharmacoresistant seizures, cognitive decline and behavioral problems. To establish the causal link between leucine-rich glioma inactivated 1 (LGI1) antibody and seizures, we developed an  antibody-mediated AE rat model in which serum antibodies (IgG) obtained from blood samples of leucine-rich glioma inactivated 1 (LGI1) protein antibody (IgG) positive encephalitis patients were passively transferred into non-epileptic Wistar rats. Serum IgG of N-methyl-d-aspartate receptor (NMDAR) antibody positive patients were used as positive control since the pathogenicity of this antibody has been previously shown in animal models.

Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis.

Patients with focal epilepsy of unknown cause (FEoUC) may display T cell infiltration in post-surgery brain specimens and increased serum levels of pro-inflammatory cytokines produced by B and T cells, indicating potential involvement of adaptive immunity. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups to find clues supporting the distinct organization of adaptive immunity in FEoUC. Twenty-two patients with FEoUC and 25 age and sex matched healthy individuals were included. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. Expression levels of anti-inflammatory cytokines and FOXP3 were measured by real-time PCR. Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay was conducted using CD4 T cells. Patients with FEoUC showed significantly decreased regulatory B (Breg), B1a, plasmablast and regulatory T (Treg) cell percentages, and increased switched memory B and Th17 cell ratios. Moreover, CD4CD25CD49d Tregs of FEoUC patients displayed significantly reduced TGFB1 and FOXP3, but increased IL10 gene expression levels. CD4 helper T cells of patients with FEoUC gave more exaggerated proliferation responses to phytohemagglutinin, anti-CD3 and anti-CD28 stimulation. Patients with FEoUC display increased effector lymphocyte, decreased regulatory lymphocyte ratios, and impaired Treg function and enhanced lymphocyte proliferation capacity. Overall, this pro-inflammatory phenotype lends support to the involvement of adaptive immunity in FEoUC.

Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy.

Multiple sclerosis (MS) may present with predominant involvement of the spinal cord and optic nerve (MS/w-SCON) and mimic other autoimmune inflammatory demyelinating disorders (AIDD) such as neuromyelitis optica spectrum disorder (NMOSD), and relapsing inflammatory optic neuritis (RION). Thus, biomarkers are required for effective differential diagnosis of AIDD.

Differentiating multiple sclerosis with predominant spinal cord and optic nerve involvement from other autoimmune demyelinating diseases using B cell immunophenotyping and gene expression profiling.

Article	Year
Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis. Frontiers in immunology\| PubMed ID: 38035091	2023
Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy. Journal of neuroimmunology\| PubMed ID: 38241950	2024
Differentiating multiple sclerosis with predominant spinal cord and optic nerve involvement from other autoimmune demyelinating diseases using B cell immunophenotyping and gene expression pr... Multiple sclerosis and related disorders\| PubMed ID: 39729902	2025

Canan Aysel Ulusoy

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