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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Multiple sclerosis (MS) often initiates with an acute episode of neurological disturbance, known as clinically isolated syndrome (CIS). There is an unmet need for biomarkers that differentiate patients who will convert to MS and who will remain as CIS after the first attack.

CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis.

 Brain-derived neurotrophic factor (BDNF) levels are reduced in advanced stages of multiple sclerosis (MS) and may be associated with reduced regenerative capability in progressive MS. This has brought increased attention to factors regulating BDNF production in MS. Our aim was to investigate the link between neurotrophin-regulating microRNAs (miRNA) and disease progression in MS.  Serum levels of BDNF and peripheral blood mononuclear cell (PBMC) expression levels of miR-132-3p, miR-106b-5p and miR-19b-3p were respectively measured by ELISA and real time PCR in twelve relapsing remitting MS (RRMS) patients, seven secondary progressive MS (SPMS) patients and fourteen healthy controls.  Serum BDNF levels were significantly reduced in SPMS patients, while selected miRNAs were significantly upregulated in PBMC of RRMS and SPMS patients. miR-106b-5p and miR-19b-3p respectively showed the highest sensitivity and specificity for MS diagnosis by receiver operating characteristic curve analysis. There was a negative correlation between levels of BDNF and the miRNAs in RRMS. Likewise, levels of BDNF and the investigated miRNAs showed positive and negative correlations respectively with the expanded disability status scale in RRMS and SPMS patients. miR-132-3p and miR-106b-5p levels showed positive correlations with the progression index in SPMS patients.  Our results suggest that increased disability is associated with downregulation of miR-132-3p, miR-106b-5p and miR-19b-3p in RRMS patients and putatively promotes increased production of neuroprotective BDNF as a compensatory mechanism. This link between the investigated miRNAs and BDNF in RRMS does not appears to hold for SPMS. This might be one of the factors contributing to reduced regenerative ability in the progressive stage of MS.

miR-132-3p, miR-106b-5p, and miR-19b-3p Are Associated with Brain-Derived Neurotrophic Factor Production and Clinical Activity in Multiple Sclerosis: A Pilot Study.

Prevalence of acute ische-mic stroke (AIS) is increased in patients with coronavirus disease 2019 (COVID-19). A proposed hypothesis is increased virus-induced propensity to hypercoagulation resulting in arterial thrombosis. Our aim was to provide evidence regarding the involvement of neutrophil extracellular trap (NET) formation (NETosis) in COVID-19 related AIS.

Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke.

Clinical exacerbations characterized with neurological symptoms are observed in around 10% of Behçet's disease (BD) patients and may culminate in severe disability. Although certain immunological factors have been associated with disease activity in neuro-Behçet's disease (NBD), biomarkers for monitoring the clinical outcome of NBD have not been properly investigated.

Cerebrospinal fluid level of neurofilament light chain is associated with increased disease activity in neuro-Behçet's disease.

West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental impairment. Demonstration of autoantibodies and cytokines in some WS patients and favorable response to immunotherapy have implicated inflammation as a putative trigger of epileptiform activity in WS. Our aim was to provide additional support for altered inflammatory responses in WS through peripheral blood immunophenotype analysis.

Distribution of peripheral blood mononuclear cell subtypes in patients with West syndrome: Impact of synacthen treatment.

Chronic inflammatory demyelinating polyneuropathy (CIDP), a common and treatable autoimmune neuropathy, is frequently misdiagnosed. The aim of this study is to evaluate the relationship between immunological markers and clinical outcome measures in a mixed cohort of patients with typical CIDP and CIDP variants at different disease stages. Twenty-three typical, 16 multifocal and five distal CIDP patients were included. Twenty-five sex and age-matched healthy controls and 12 patients with Charcot-Marie-Tooth type 1A (CMT1A) disease served as controls. Peripheral B-cell populations were analyzed by flow cytometry. IL6, IL10, TNFA mRNA and mir-21, mir-146a, and mir-155-5p expression levels were evaluated by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) and/or skin biopsy specimens. Results were then assessed for a possible association with clinical disability scores and intraepidermal nerve fiber densities (IENFD) in the distal leg. We detected a significant reduction in naive B cells (P ≤ 0.001), plasma cells (P ≤ 0.001) and regulatory B cells (P < 0.05), and an elevation in switched memory B cells (P ≤ 0.001) in CIDP compared to healthy controls. CMT1A and CIDP patients had comparable B-cell subset distribution. CIDP cases had significantly higher TNFA and IL10 gene expression levels in PBMC compared to healthy controls (P < 0.05 and P ≤ 0.01, respectively). IENFDs in the distal leg showed a moderate negative correlation with switched memory B-cell ratios (r = -0.51, P < 0.05) and a moderate positive correlation with plasma cell ratios (r = 0.46, P < 0.05). INCAT sum scores showed a moderate positive correlation with IL6 gene expression levels in PBMC (r = 0.54, P < 0.05). Altered B-cell homeostasis and IL10 and TNFA gene expression levels imply chronic antigen exposure and overactivity in the humoral immune system, and seem to be a common pathological pathway in both typical CIDP and CIDP variants.

Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes.

Muscle specific kinase (MuSK) antibody positive myasthenia gravis (MG) often presents with a severe disease course and resistance to treatment. Treatment-refractory patients may respond to B cell depleting treatment methods. Our aim was to investigate whether inhibition of Fc receptor-like B (FCRLB) could effectively suppress autoimmunity without diminishing B cell counts in animal model of MG, a classical antibody-mediated autoimmune disease.

Silencing of FCRLB by shRNA ameliorates MuSK-induced EAMG in mice.

Sepsis-induced acute kidney injury is a fatal, potentially reversible clinical condition. C5a receptor (C5aR) has been implied to play pivotal roles in both autophagy and sepsis-induced organ dysfunction. The aim of this study was to demonstrate the effects of intravenous immunoglobulin preparations on the expression of autophagy markers and investigate possible association between C5aR expression and autophagy in the kidney tissue of septic rats.

Renal Expression Levels of C5a Receptor and Autophagy-related Beclin-1 and LC3A/B Are Simultaneously Enhanced Under Immunoglobulin Treatment in a Rat Model of Sepsis.

The role of synaptic dysfunction in focal epilepsy of unknown cause is not well understood. Neurogranin is a post-synaptic protein used as a biomarker of synaptic disintegration in patients with dementia.

Article	Year
CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis. Multiple sclerosis and related disorders\| PubMed ID: 33352356	2021
miR-132-3p, miR-106b-5p, and miR-19b-3p Are Associated with Brain-Derived Neurotrophic Factor Production and Clinical Activity in Multiple Sclerosis: A Pilot Study. Genetic testing and molecular biomarkers\| PubMed ID: 34788141	2021
Increased serum citrullinated histone H3 levels in COVID-19 patients with acute ischemic stroke. Ideggyogyaszati szemle\| PubMed ID: 35819341	2022
Cerebrospinal fluid level of neurofilament light chain is associated with increased disease activity in neuro-Behçet's disease. Turkish journal of medical sciences\| PubMed ID: 36326394	2022
Distribution of peripheral blood mononuclear cell subtypes in patients with West syndrome: Impact of synacthen treatment. Immunology letters\| PubMed ID: 37459957	2023
Disease activity in chronic inflammatory demyelinating polyneuropathy: association between circulating B-cell subsets, cytokine levels, and clinical outcomes. Clinical and experimental immunology\| PubMed ID: 37638717	2024
Silencing of FCRLB by shRNA ameliorates MuSK-induced EAMG in mice. Journal of neuroimmunology\| PubMed ID: 37660538	2023
Renal Expression Levels of C5a Receptor and Autophagy-related Beclin-1 and LC3A/B Are Simultaneously Enhanced Under Immunoglobulin Treatment in a Rat Model of Sepsis. In vivo (Athens, Greece)\| PubMed ID: 40010959	2025
Treatment-resistant patients with focal epilepsy of unknown cause display reduced neurogranin levels: a preliminary study. Ideggyogyaszati szemle\| PubMed ID: 40476457	2025

Gizem Koral

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