Neuroimmunological Research Research Articles

Astrocyte-derived Interleukin-31 causes poor prognosis in elderly patients with intracerebral hemorrhage.

The incidence of intracerebral hemorrhage (ICH) is increasing every year, with very high rates of mortality and disability. The prognosis of elderly ICH patients is extremely unfavorable. Interleukin, as an important participant in building the inflammatory microenvironment of the central nervous system after ICH, has long been the focus of neuroimmunology research. However, there are no studies on the role IL31 play in the pathologic process of ICH. We collected para-lesion tissue for immunofluorescence and flow cytometry from the elderly and young ICH patients who underwent surgery. Here, we found that IL31 expression in the lesion of elderly ICH patients was significantly higher than that of young patients. The activation of astrocytes after ICH releases a large amount of IL31, which binds to microglia through IL31R, causing a large number of microglia to converge to the hematoma area, leading to the spread of neuroinflammation, apoptosis of neurons, and ultimately resulting in poorer recovery of nerve function. Interfering with IL31 expression suppresses neuroinflammation and promotes the recovery of neurological function. Our study demonstrated that elderly patients release more IL31 after ICH than young patients. IL31 promotes the progression of neuroinflammation, leading to neuronal apoptosis as well as neurological decline. Suppression of high IL31 concentrations in the brain after ICH may be a promising therapeutic strategy for ICH.

Is anti-NMDA receptor encephalitis real? I. Diagnostic challenges

After conducting a thorough analysis of clinical, neurophysiological, neuroimmunological, neurobiological, and neuropathological research findings, the authors of the review question on the validity of the anti-NMDA receptor encephalitis concept. The review highlights the significance of studying sanogenetic mechanisms in medicine and warns against hasty interpretations of neurobiological data without clinical knowledge.

A Comprehensive Review on Neuroimmunology: Insights from Multiple Sclerosis to Future Therapeutic Developments.

This review delves into neuroimmunology, focusing on its relevance to multiple sclerosis (MS) and potential treatment advancements. Neuroimmunology explores the intricate relationship between the immune system and the central nervous system (CNS). Understanding these mechanisms is vital for grasping the pathophysiology of diseases like MS and for devising innovative treatments. This review introduces foundational neuroimmunology concepts, emphasizing the role of immune cells, cytokines, and blood-brain barrier in CNS stability. It highlights how their dysregulation can contribute to MS and discusses genetic and environmental factors influencing MS susceptibility. Cutting-edge research methods, from omics techniques to advanced imaging, have revolutionized our understanding of MS, offering valuable diagnostic and prognostic tools. This review also touches on the intriguing gut-brain axis, examining how gut microbiota impacts neuroimmunological processes and its potential therapeutic implications. Current MS treatments, from immunomodulatory drugs to disease-modifying therapies, are discussed alongside promising experimental approaches. The potential of personalized medicine, cell-based treatments, and gene therapy in MS management is also explored. In conclusion, this review underscores neuroimmunology's significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes.

Neuronal binding by antibodies can be influenced by low pH stress during the isolation procedure

Low pH stress and its influence on antibody binding is a common consideration among chemists, but is only recently emerging as a consideration in Immunological studies. Antibody characterizations in Multiple Sclerosis (MS), an autoimmune disease of the Central Nervous System (CNS) has revealed that antibodies in the cerebrospinal fluid (CSF) of patients with Multiple Sclerosis bind to myelin-related and non-myelin antigen targets. Many laboratories have used molecular biology techniques to generate recombinant human antibodies (rhAbs) expressed by individual B cells from healthy donors and patients with systemic autoimmune disease to identify antigen targets. This approach has been adapted within the Neuroimmunology research community to investigate antigen targets of individual B cells in the CSF of MS patients. Our laboratory determines which antibodies to clone based on their immunogenetics and this method enriches for cloning of rhAbs that bind to neurons. However, newer technologies to assist in purification of these rhAbs from culture supernatants use an acidic elution buffer which may enhance low pH stress on the antibody structure. Our laboratory routinely uses a basic elution buffer to purify rhAbs from culture supernatants to avoid low pH stress to the antibody structure. Our goal was to investigate whether acidic elution of our rhAbs using Next Generation Chromatography would impact the rhAbs' ability to bind neurons. The limited data presented here for two neuron-binding rhAbs tested indicated that acidic elution buffers used during rhAb purification impacted the ability of rhAbs with low CDR3 charge to maintain binding to neuronal targets. Reproducibility in a larger panel of rhAbs and factors underlying these observations remain untested.

Metabolomic Profiling of Multiple Sclerosis Lesions and Periplaque White Matter Demonstrates Extensive Changes in Lipid Metabolism (P2-3.010)

<h3>Objective:</h3> To identify whether there are differences between the brain tissue metabolome in people with multiple sclerosis (PwMS) compared to controls and between the different type of MS lesions <h3>Background:</h3> MS is characterized by immune-mediated white matter (WM) demyelination and consecutive axonal loss. Whether this process alters the metabolome in the affected brain areas is not clear. <h3>Design/Methods:</h3> Brain tissues, obtained from 5 PwMS and 12 controls, were sent for metabolomic analysis. In PwMS, tissues were extracted from the edge and core of demyelinated WM chronic active and inactive lesions, and periplaque WM, while in controls they were dissected from normal WM. Weighted gene correlation network analysis (WGCNA) were utilized to cluster highly correlated metabolites together into modules. We then applied generalized estimating equations models to compare WGCNA-module scores between different tissues, accounting for multiple metabolomic profiles contributed by some subjects. <h3>Results:</h3> MS lesions were found to have decreased concentrations of hexosylceramides (p = 0.019), glycero-phospholipids (p = 3.6E−7), nucleotide metabolites (p = 5.0E−4), and long-chain fatty acids (p = 1.6E−6) and increased concentrations of dipeptides/sugars (p = 0.0063), sphingosines (p = 0.0026), phospholipids (p = 0.0019), sphingomyelines and ceramides (p = 4.4E−10) compared to control WM. In MS periplaques there were decreased levels of glycerol-phospholipids (p = 0.017) and long-chain fatty acids (p = 0.014) and increased levels of sphingomyelines and ceramides (p = 0.0026) compared to control WM. <h3>Conclusions:</h3> Myelin lipids were significantly altered in MS with more prominent differences in lesions, and these could potentially act as biomarkers of inflammation and neurodegeneration in PwMS. <b>Disclosure:</b> Dr. Ladakis has nothing to disclose. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. The institution of Dr. Absinta has received research support from International MS Alliance. The institution of Dr. Absinta has received research support from FRRB Early Career Award. The institution of Dr. Absinta has received research support from Cariplo Foundation. Dr. Reyes-Mantilla has nothing to disclose. The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research . The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

Myelitis and Myelopathies in the Era of COVID-19 (P4-10.003)

<h3>Objective:</h3> To characterize the clinical presentations of myelitis and myelopathies following SARS-CoV2 infection (COVID-19) or vaccination for COVID-19. <h3>Background:</h3> Neurologic complications of COVID-19 are well-described; however, myelopathies associated with COVID-19 are comparatively rarer events. Myelopathies associated with vaccination are even rarer than those seen with infection. There is a need to recognize and document these rare cases as the number of infections and vaccinations increase to refine diagnosis and treatment. <h3>Design/Methods:</h3> We reviewed the clinical profiles of 15 patients referred to the Johns Hopkins Myelitis &amp; Myelopathy Center between April 2020 and June 2022 for myelopathic syndromes suspected to be triggered by SARS-CoV-2 infection or COVID-19 vaccination. Each patient’s etiology was classified as vascular, inflammatory, unmasking of neurological disease, or unknown. <h3>Results:</h3> All vascular myelopathies (n=5) were associated with COVID-19 and presented as acute and subacute progressive bladder dysfunction and weakness with non-enhancing lesions on MRI. Inflammatory myelopathies were associated with vaccination (n=3) and COVID-19 (n=2) and were notable for CSF pleocytosis, elevated protein, and involvement of white matter tracts and grey matter on MRI. COVID-19 and vaccination were associated with unmasking underlying myelopathic disease (e.g., demyelinating or metabolic) in 4 patients. Among the vaccination group (n=5), 2 received one dose of the mRNA-1273 vaccine and 3 received one dose of the Ad26.COV2.S vaccine. One patient could not be classified. <h3>Conclusions:</h3> Initial imaging in vascular patients had subtle findings recognized in hindsight–early recognition on imaging could refine differential diagnosis. Patients with inflammatory etiologies generally only saw improvement in their symptoms after PLEX; early initiation can halt progression and improve outcomes. Among the unmasked group, patients had heterogeneous clinical presentations. Imaging in this group showed chronic lesions, unlike the other two groups. It is critical to identify the etiological factors in subjects with myelopathies in the setting of COVID-19 or vaccination to establish an appropriate treatment. <b>Disclosure:</b> Ms. Hao has nothing to disclose. Dr. Dominguez Penuela has nothing to disclose. Dr. Reyes-Mantilla has nothing to disclose. The institution of Dr. Barreras has received research support from Foundation for Sarcoidosis Research. The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research .

Natural IgG Anti-F (ab')2 Autoantibody Activity in Children with Autism.

Background: Many and diverse autoimmune abnormalities have been reported in children with autism. Natural autoantibodies (NAAbs) play important immunoregulatory roles in recognition of the immune self. The objective of this study was to examine the presence of NAAbs in the sera of children with autism and across severity subgroups of autistic behavioral impairments. Methods: NAAbs were titrated in sera through an ELISA procedure in 60 low-functioning children with autism and 112 typically developing controls matched for age, sex and puberty. Results: Serum titers of IgG anti-F(ab')2 autoantibodies were significantly lower in children with autism compared to typically developing controls (p < 0.0001), and were significantly negatively associated with autism severity (p = 0.0001). This data appears to be related more specifically to autism than to intellectual disability, given that IgG anti-F(ab')2 levels were significantly negatively correlated with IQ scores in the autism group (p = 0.01). Conclusions: This is the first report in autism of abnormally low natural anti-F(ab')2 autoantibody activity. The findings suggest a dysfunction of self-recognition mechanisms which may play a role in the pathogenesis of autism, especially for the severely affected children. These findings strengthen the hypothesis of an autoimmune process in autism and open the prospect of alternative medical treatment. Further neuroimmunological research is warranted to understand the exact mechanisms underlying this reduced natural IgG anti-F (ab')2 autoantibody activity, and to assess its impact on the pathophysiology and behavioral expression of autism.

The future of neuroimmunology research for CNS disease therapeutics

It is an exciting time to be in neuroimmunology research. Promising pharmacological targets and drug approaches for the treatment of diseases of the central nervous system (CNS) are emerging. Jerry Madukwe, the Editor-in-Chief of Trends in Pharmacological Sciences asked authors of the August 2022 special issue to reflect on the global challenges in the field and what they see as the future of neuroimmunology research for CNS disease therapy.

MGEnrichment: A web application for microglia gene list enrichment analysis.

Gene expression analysis is becoming increasingly utilized in neuro-immunology research, and there is a growing need for non-programming scientists to be able to analyze their own genomic data. MGEnrichment is a web application developed both to disseminate to the community our curated database of microglia-relevant gene lists, and to allow non-programming scientists to easily conduct statistical enrichment analysis on their gene expression data. Users can upload their own gene IDs to assess the relevance of their expression data against gene lists from other studies. We include example datasets of differentially expressed genes (DEGs) from human postmortem brain samples from Autism Spectrum Disorder (ASD) and matched controls. We demonstrate how MGEnrichment can be used to expand the interpretations of these DEG lists in terms of regulation of microglial gene expression and provide novel insights into how ASD DEGs may be implicated specifically in microglial development, microbiome responses and relationships to other neuropsychiatric disorders. This tool will be particularly useful for those working in microglia, autism spectrum disorders, and neuro-immune activation research. MGEnrichment is available at https://ciernialab.shinyapps.io/MGEnrichmentApp/ and further online documentation and datasets can be found at https://github.com/ciernialab/MGEnrichmentApp. The app is released under the GNU GPLv3 open source license.

Pathways linking Alzheimer’s disease risk genes expressed highly in microglia

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Neuroprotective effect of edible bird’s nest in chronic cerebral hypoperfusion induced neurodegeneration in rats

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Intestinal inflammation and compromised barrier function in idiopathic parkinsonism: scenario captured by systematic review

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Immovable Object Meets Unstoppable Force? Dialogue Between Resident and Peripheral Myeloid Cells in the Inflamed Brain.

Inflammation of the brain parenchyma is characteristic of neurodegenerative, autoimmune, and neuroinflammatory diseases. During this process, microglia, which populate the embryonic brain and become a permanent sentinel myeloid population, are inexorably joined by peripherally derived monocytes, recruited by the central nervous system. These cells can quickly adopt a morphology and immunophenotype similar to microglia. Both microglia and monocytes have been implicated in inducing, enhancing, and/or maintaining immune-mediated pathology and thus disease progression in a number of neuropathologies. For many years, experimental and analytical systems have failed to differentiate resident microglia from peripherally derived myeloid cells accurately. This has impeded our understanding of their precise functions in, and contributions to, these diseases, and hampered the development of novel treatments that could target specific cell subsets. Over the past decade, microglia have been investigated more intensively in the context of neuroimmunological research, fostering the development of more precise experimental systems. In light of our rapidly growing understanding of these cells, we discuss the differential origins of microglia and peripherally derived myeloid cells in the inflamed brain, with an analysis of the problems resolving these cell types phenotypically and morphologically, and highlight recent developments enabling more precise identification.

Editorial: Update on Translational Neuroimmunology - Research of ISNI 2018.

With its roots firmly planted in the fields of CNS autoimmunity and infection, the rapidly growing field of neuroimmunology is branching out to include almost every area of neurophysiology and neurological disease to encompass brain development and function, psychiatric illnesses, inflammatory demyelinating diseases, cancer, infections and neurodegeneration of the central and peripheral nervous systems. The nervous system is also functionally intimately interconnected, via immune mechanisms, to multiple other processes and organ systems including systemic inflammation, gut microbiome, and chronic pain, to name a few. The scope of neuroimmunology and its implications for the understanding of human health and disease, from diagnosis through therapeutics, was highlighted during the 14th Congress of the International Society for Neuroimmunology (ISNI) 2018, and the associated 2nd Global Schools of Neuroimmunology (GSNI), held together in August 2018 in Brisbane, Australia. The richness of topics covered is further illustrated through the series of related articles presented in this special issue of Frontiers in Neurology entitled ‘Update on Translational Neuroimmunology Research of ISNI 2018’.

Resection of orthotopic murine brain glioma

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

The immune regulation of PD-1/PDL-1 axis, a potential biomarker in multiple sclerosis

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Resolution of inflammation and repair after ischemic brain injury

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Clinical efficacy and safety of single cycle rituximab as induction therapy for aggressive neuromyelitis optica spectrum disorder in a resource limited center: a preliminary study

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.

Defining activation states of microglia in human brain tissue: an unresolved issue for Alzheimer’s disease

Neuroimmunology and Neuroinflammation is an open access journal, with focuses on neuroimmunology and neuroinflammation research, and coverage extending to other basic and clinical studies related to neuroscience.