Autoimmune Neurological Disorders Research Articles

Renal disease associated with multiple sclerosis: A narrative review.

Multiple sclerosis (MS) is a chronic autoimmune neurological disorder characterized by central nervous system demyelination, leading to various neurological impairments. While the primary focus of research and clinical management has centered on the neurological aspects of MS, emerging evidence suggests a complex interplay between MS and renal disease. This narrative review endeavors to elucidate the intriguing association between MS and renal disease, providing a comprehensive overview of the current knowledge on this topic. Our review begins by outlining the pathophysiology of MS and the diverse mechanisms contributing to its progression. We then delve into renal disease, categorizing the various types and their clinical presentations. This review focuses on exploring the intricate relationship between these seemingly distinct conditions. We analyze existing literature to uncover shared risk factors, potential pathophysiological links, and the impact of MS on renal function. Furthermore, we discuss the clinical presentation and diagnostic challenges in identifying renal disease in MS patients. Importantly, we examine available treatment options and their efficacy in managing renal complications in this unique patient population. The consequences of renal disease on the overall quality of life (QOL) for individuals living with MS are also examined, shedding light on the multifaceted burden of these coexisting conditions.

Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

FcRn Inhibitor Therapies in Neurologic Diseases.

In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases.

Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population. We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls. Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10-8, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 (p = 4.36 × 10-7; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 (p = 1.28 × 10-8; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQβ1-126H (p = 1.43 × 10-12; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R (p = 3.40 × 10-8; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02. Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

The role of the "gut microbiota-mitochondria" crosstalk in the pathogenesis of multiple sclerosis.

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

Dental Adverse Effects of Anti-CD20 Therapies.

Over the past few years, anti-CD20 therapies like rituximab, ocrelizumab or ofatumumab have seen an increase in interest in the treatment of neurological autoimmune disorders such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), or resistant forms of generalized myasthenia gravis (MG). They are generally well-tolerated, but recent reports have highlighted severe dental disorders in patients undergoing anti-CD20 therapies. The aim was to describe a series of cases and to compare with the available scientific literature. We reviewed 6 patient cases with dental disorders during anti-CD20 therapy that were reported to the pharmacovigilance center. A disproportionality analysis was also conducted on Vigibase® for each anti-CD20 and each adverse effect described in the cases. Six cases of dental and gingival conditions in relatively young patients were reported (median age: 40.5 years old [min: 34; max: 79]). Oral conditions were developed in four patients with MS treated with ocrelizumab and in two patients receiving rituximab (one patient with MG and one with NMOSD). The onset of oral conditions ranged from 10 days to 2 years after treatment initiation. Notably, all patients treated with ocrelizumab experienced gingival recession. Various dental pathologies were observed, including tooth loss, dental pain, caries, brittle teeth, dental fractures, dental abscesses, and periodontitis. Analysis of Vigibase® revealed 284 worldwide cases of dental and gingival conditions under ocrelizumab, 386 cases under rituximab, and 80 under ofatumumab. Significant associations were found between these therapies and dental pathologies, particularly tooth abscesses and infections. To our knowledge, this is the first case series reporting dental conditions developed in patients long-term treated with anti-CD20 treatments. This issue, literature data, and Vigilyze® analysis might be considered a safety signal that necessitates being confirmed with more robust data, such as a retrospective study with a control group. Meanwhile, proactive measures are essential like frequent dental checkups and dental hygienic measures to prevent oral health problems associated with anti-CD20 therapies.

Gut microbiota and autoimmune neurologic disorders: a two-sample bidirectional Mendelian randomization study.

Increasing evidence has suggested that alterations in the gut microbiome are correlated with autoimmune neurologic disorders, yet the causal relationship between them has yet to be established. From the published genome-wide association study (GWAS) summary statistics, we obtained data on the gut microbiota and three autoimmune neurologic disorders (Multiple Sclerosis, Guillain-Barré Syndrome, and Myasthenia Gravis). We then implemented a two-sample Mendelian Randomization (MR) to determine the causal relationship between the gut microbiota and the diseases. To validate the results, we conducted a series of sensitivity analyses. Finally, to verify the direction of causality, a reverse-causality analysis was done. We discovered that a higher relative abundance of the genus Ruminococcus2 (OR: 1.213, 95% CI: 1.006-1.462, p = 0.043, PFDR = 0.048) and the genus Roseburia (OR: 1.255, 95% CI: 1.012-1.556, p = 0.038, PFDR = 0.048) were associated with a higher risk of MS. Furthermore, the higher the abundance of the class Mollicutes (OR: 3.016, 95% CI: 1.228-7.411, p = 0.016, PFDR = 0.021), the genus Eubacterium (hallii group) (OR: 2.787, 95% CI: 1.140-6.816, p = 0.025, PFDR = 0.025), and the phylum Tenericutes (OR: 3.016, 95% CI: 1.228-7.411, p = 0.016, PFDR = 0.021) was linked to a greater probability of GBS. Additionally, the higher the abundance of the genus Ruminococcaceae UCG005 (OR: 2.450, 95% CI: 1.072-5.598, p = 0.034, PFDR = 0.036), the genus Holdemania (OR: 2.437, 95% CI: 1.215-4.888, p = 0.012, PFDR = 0.024), genus Lachnoclostridium (OR: 3.681, 95% CI: 1.288-10.521, p = 0.015, PFDR = 0.025) and the genus Eubacterium (ruminantium group) (OR: 2.157, 95% CI: 1.211-3.843, p = 0.003, PFDR = 0.016) correlated with a greater chance of MG occurrence. No SNPs were identified as outliers through sensitivity analysis. Then, the results of the reverse MR analysis did not indicate any reverse causality. Our findings demonstrate a causal relationship between the gut microbiota and three autoimmune neurologic disorders, providing novel insights into the mechanisms of these autoimmune neurologic disorders that are mediated by gut microbiota.

DEEP-EP: Identification of epigenetic protein by ensemble residual convolutional neural network for drug discovery

Epigenetic proteins (EP) play a role in the progression of a wide range of diseases, including autoimmune disorders, neurological disorders, and cancer. Recognizing their different functions has prompted researchers to investigate them as potential therapeutic targets and pharmacological targets. This paper proposes a novel deep learning-based model that accurately predicts EP. This study introduces a novel deep learning-based model that accurately predicts EP. Our approach entails generating two distinct datasets for training and evaluating the model. We then use three distinct strategies to transform protein sequences to numerical representations: Dipeptide Deviation from Expected Mean (DDE), Dipeptide Composition (DPC), and Group Amino Acid (GAAC). Following that, we train and compare the performance of four advanced deep learning models algorithms: Ensemble Residual Convolutional Neural Network (ERCNN), Generative Adversarial Network (GAN), Convolutional Neural Network (CNN), and Gated Recurrent Unit (GRU). The DDE encoding combined with the ERCNN model demonstrates the best performance on both datasets. This study demonstrates deep learning's potential for precisely predicting EP, which can considerably accelerate research and streamline drug discovery efforts. This analytical method has the potential to find new therapeutic targets and advance our understanding of EP activities in disease.

Describe the Clinical Course, Diagnostic Approach and Outcomes Following Thymectomy in Four Non-myasthenic Patients with Synaptic Antibody-mediated Autoimmune Neurologic Disease (P4-14.001)

Describe the Clinical Course, Diagnostic Approach and Outcomes Following Thymectomy in Four Non-myasthenic Patients with Synaptic Antibody-mediated Autoimmune Neurologic Disease (P4-14.001)

Polygenic risk associated with Alzheimer's disease and other traits influences genes involved in T cell signaling and activation.

T cells, known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. T cell gene expression phenotypes can be regulated by disease-associated genetic variants. Many complex diseases are better represented by polygenic risk than by individual variants. We first compute a polygenic risk score (PRS) for Alzheimer's disease (AD) using genomic sequencing data from a cohort of Alzheimer's disease (AD) patients and age-matched controls, and validate the AD PRS against clinical metrics in our cohort. We then calculate the PRS for several autoimmune disease, neurological disorder, and immune function traits, and correlate these PRSs with T cell gene expression data from our cohort. We compare PRS-associated genes across traits and four T cell subtypes. Several genes and biological pathways associated with the PRS for these traits relate to key T cell functions. The PRS-associated gene signature generally correlates positively for traits within a particular category (autoimmune disease, neurological disease, immune function) with the exception of stroke. The trait-associated gene expression signature for autoimmune disease traits was polarized towards CD4+ T cell subtypes. Our findings show that polygenic risk for complex disease and immune function traits can have varying effects on T cell gene expression trends. Several PRS-associated genes are potential candidates for therapeutic modulation in T cells, and could be tested in in vitro applications using cells from patients bearing high or low polygenic risk for AD or other conditions.

Review of Satralizumab for Neuromyelitis Optica Spectrum Disorder: A New Biologic Agent Targeting the Interleukin-6 Receptor.

Currently, three monoclonal antibodies (MABs) have received regulatory approval from the federal agency, the United States Food and Drug Administration (USFDA), for the medical management of neuromyelitis optica spectrum disorder (NMOSD). Satralizumab was the third approved therapy after MABs like eculizumab and inebilizumab for NMOSD, an uncommon but severe enfeebling autoimmune neurological disease. Satralizumab, a humanized monoclonal antibody, exerts its action in NMOSD by acting against cytokine interleukin-6 (IL-6), a foremost mediator in the pathological process of NMOSD. Two pivotal clinical trials carried out in NMOSD patients had established that satralizumab significantly decreased the rate of relapse in patients suffering from NMOSD as opposed to placebo. The trials also demonstrated that satralizumab is relatively safe. Thus, satralizumab provides an efficacious and safe treatment option for this rare, disabling central nervous system (CNS) disease. Our review aimed to elucidate the pharmacological characteristics of satralizumab and illustrate the available evidence regarding its safety and efficacy in patients with NMOSD.

Attention Deficit/Hyperactivity Disorder in Children with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurological autoimmune disease; pediatric-onset multiple sclerosis (POMS) represents 5% to 10% of total MS population. Children with POMS may experience attention difficulties due to the disease's impact on the central nervous system. However, little is known regarding Attention Deficit Hyperactivity Disorder (ADHD) in POMS, and its relation to cognitive performance. A retrospective case review was conducted using medical records of 66 children and adolescent patients diagnosed with POMS between 2012 and 2021 in a MS center of a tertiary medical center. All patients had undergone routine clinical neurological examinations and had been assessed for a diagnosis of ADHD by a department pediatric neurologist. In addition, sociodemographic data, disease-related variables, and cognitive performance were collected. Of the 66 patients, 31 (47%) had a diagnosis of ADHD; 29 (44%) had cognitive impairment. Moreover, we identified four different profiles of POMS: those with only ADHD (17, 26%); only cognitive impairment (15, 23%), ADHD and cognitive impairment (14, 21%), and only POMS (20, 30%). A significant difference in disease duration was found among the four profiles [F(3,65) = 8.17, p < .001, η² = 0.29], indicating that patients with ADHD and cognitive impairment were characterized by longer disease duration. ADHD may be prominently involved in POMS, even during the early stages of the disease and early diagnosis is crucial in order to provide appropriate interventions and support.

Real-world data on the Immunity Response to the COVID-19 Vaccine among Patients with Central Nervous System Immunological Diseases

Objective: The effects of immunotherapies on the immune response to various regimens of SARS-CoV-2 vaccines in patients with autoimmune neurological disease have been demonstrated in limited data. Thus, we evaluated the immune responses in each platform of COVID-19 vaccination between patients with autoimmune neurological disease and a healthy population. Materials and Methods: We conducted a prospective observational study. We collected serum from patients with autoimmune neurological diseases to perform serological methods using anti-RBD IgG assay, neutralizing antibodies assay, and interferon SARS-CoV-2 immunoassay. Serological response level was analyzed by platforms of vaccines and types of immune modifying therapy. Results: Fifty-eight patients had tested for an anti-RBD IgG response, and those receiving no immunotherapy/ healthy controls had the highest median anti-RBD IgG levels amongst immunotherapy statuses. Rituximab in those who received inactivated or mRNA vaccine regimens had the lowest antibody level compared with other immunotherapies. In vector-based vaccine regimens, significant reductions of anti-RBD IgG response were observed in all other immunotherapy groups except for azathioprine, with the greatest difference seen compared to rituximab. Thirty-five patients with positive anti-RBD responses were further tested for neutralizing antibodies. The mRNA vaccine regimen demonstrated the highest inhibition percentage among the Delta and Omicron variants. Twentytwo patients were tested for T cell responses, with no significant difference in T-cell activity across all groups. Conclusion: We have demonstrated a significant decrease in antibody response against SARS-CoV-2 in patients with autoimmune neurological diseases receiving immunotherapies compared to a healthy population, especially for patients taking rituximab.

Folate receptor alpha autoantibodies in the serum of patients with relapsing–remitting multiple sclerosis (RRMS)

Multiple sclerosis (MS) is a potentially progressive, autoimmune neurologic disorder of the central nervous system (CNS), resulting from an autoimmune attack on central nervous system white matter. Folate deficiencies are linked to DNA instability and breakdown of phospholipid membranes and thus might affect myelin integrity. Folic acid exerts its effects through its receptors (FRs). Folate receptor alpha autoantibodies (FRAA) can block folate transport to the brain. Due to important role of folate in the pathogenesis of MS, in this project we aimed to study FRAA serum levels in patients with relapsing remitting multiple sclerosis (RRMS). Fifty-four patients with RRMS and 58 healthy individuals were enrolled in this study. Serum samples were collected from all participants and folate receptor alpha autoantibody (FRAA) serum concentration was measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that FRAA serum levels in patients with RRMS is 67.20±19.79ng/ml as compared to controls which was 37.32±13.26ng/ml. Significant increase in folate receptor autoantibody serum concentration was seen in patients with RRMS when compared to control group (P=0.007). The results showed that a high concentration of folate receptor autoantibody is associated with RRMS. We have also found that 85.18% (46/54) of patients with RRMS were positive for serum FRAA, whereas the prevalence in controls was only 46.55% (27/58). It is concluded that serum FRAA are more prevalent in RRMS patients than controls. The findings also suggest that FRAA might be involved in the pathophysiology of RRMS.

Effectiveness of Therapeutic Plasma Exchange in Autoimmune Neurological Diseases in a Tertiary Care Hospital of South India

ABSTRACT Background and Objectives: Therapeutic plasma exchange (TPE) is commonly used as a treatment of certain autoimmune neurological diseases, and its main target is to remove pathogenical toxins or autoantibodies. Removed plasma with toxins and autoantibodies is replaced by crystalloids, colloids, and/or normal saline. It is more effective and cost-effective than immunoglobulins. The aim of this study was to know the effectiveness of TPE in autoimmune neurological diseases. Methods: This is a prospective study involving 376 autoimmune neurological cases, and the duration of this study was 5 years. All autoimmune neurological patients irrespective of age with complaints of weakness in limbs, respiratory distress, and acute myasthenia gravis (MG) crisis cases were included in the study. The Modified Rankin Score and MG Composite Score were used to analyze the severity of the disease, and the number of TPE procedures or cycles was planned. Results: The total number of cases included was 376 (322 newly registered cases and 54 old and relapse cases), and the total number of TPE procedures done was 1491 between the years 2017 and 2021. Male patients were 138 and female patients 238. The most number of cases were of MG, followed by Guillain–Barre syndrome. The mean number of TPE procedures done was 6.1 cycles in myasthenia crisis patients. There was a significant improvement in the patients after the treatment. The Modified Rankin Score and MG Composite Score were 1/6 and 3/50, respectively (P = 0.0321 and P = 0.0298, respectively) after completion of the TPE. Conclusion: TPE is the most effective method in cases of neurological autoimmune diseases. Most of the cases show improvement immediately after the first cycle, and more than half of the cases will be able to walk or do their routine activities after 2 or 3 cycles. It is a safe and cost-effective treatment modality with minimal side effects or complications.

Clinical characteristics of seizure-predominant autoimmune encephalitis and utility of anti-neuronal antibody scores for early treatment

We analyzed 20 patients diagnosed with autoimmune neurological diseases with seizure predominance. In these patients, we examined the usefulness of Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) score in autoimmune encephalitis (AE) for facilitating early treatment. APE2 score was positive in 19 of 20 patients. ACES score was positive in 15 of 20 patients, and 4 of 5 of the patients with negative ACES score did not have AE. Comprehensive assessment including the use of the above scores is desirable in the early stage of AE.

Antibody Response to HERV-K and HERV-W Envelope Epitopes in Patients with Myasthenia Gravis.

Myasthenia gravis is an antibody-mediated autoimmune neurological disorder characterized by impaired neuromuscular junction transmission, resulting in muscle weakness. Recently, the involvement of Human Endogenous Retroviruses (HERVs) in the pathophysiology of different immune-mediated and neurodegenerative diseases, such as multiple sclerosis, has been demonstrated. We aimed to investigate potential immune system involvement related to humoral responses targeting specific epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis. Myasthenia gravis patients were recruited in the Neurology Unit, while healthy controls were selected from the Blood Transfusion Center, both affiliated with AOU Sassari. Highly immunogenic antigens of HERV-K and HERV-W envelope proteins were identified using the Immune Epitope Database (IEDB) online tool. These epitopes were utilized in enzyme-linked immunosorbent assays (ELISA) to detect autoantibodies in serum directed against these sequences. The study involved 39 Healthy Donors and 47 MG patients, further categorized into subgroups based on the presence of autoantibodies: MG-AchR Ab+ (n = 17), MG-MuSK Ab+ (n = 7), double seronegative patients (MG-DSN, n = 18), MG-LRP4 Ab + (n = 4), and one patient with no antibodies data (n = 1). Our findings revealed high levels of autoantibodies in myasthenia gravis patients directed against the HERV-K-env-su(19-37), HERV-K-env-su(109-126), HERV-K-env-su(164-186), HERV-W-env(93-108), HERV-W-env(129-14), and HERV-W-env(248-262) epitopes. Notably, these results remained highly significant even when patients were subdivided into MG-AchR Ab+ and MG-DSN subgroups. Correlation analysis further revealed significant positive associations between the antibody levels against HERV-K and HERV-W families in patients, suggesting a synergistic action of the two HERVs in the pathology context since this correlation is absent in the control group. This study marks the first identification of a specific humoral response directed against defined epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis patients. These findings lay the foundation for future investigations aimed at elucidating the molecular mechanisms driving this immune response. The detection of these autoantibodies suggests the potential for novel biomarkers, especially within the MG-DSN patient subgroup, addressing the need for new biomarkers in this population.

Safety of SARS-CoV-2 vaccine in patients with autoimmune neurological conditions: A systematic review and meta-analysis

IntroductionRisk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. MethodsElectronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. ResultsTwenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27–0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18–0.36, I2 = 98 %), 0.16(0.11–0.21, I2 = 93 %), 0.15(0.00–0.31, I2 = 97 %), 0.13(0.08–0.19, I2 = 97 %), 0.11(0.07–0.15, I2 = 95 %), 0.11(0.07–0.16, I2 = 97 %), and 0.09 (0.03–0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04–0.07, I2 = 84 %). ConclusionAccording to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

Pathophysiological Effects of Autoantibodies in Autoimmune Encephalitides.

The heterogeneity of autoantibody targets in autoimmune encephalitides presents a challenge for understanding cellular and humoral pathophysiology, and the development of new treatment strategies. Thus, current treatment aims at autoantibody removal and immunosuppression, and is primarily based on data generated from other autoimmune neurological diseases and expert consensus. There are many subtypes of autoimmune encephalitides, which now entails both diseases with autoantibodies targeting extracellular antigens and classical paraneoplastic syndromes with autoantibodies targeting intracellular antigens. Here, we review the current knowledge of molecular and cellular effects of autoantibodies associated with autoimmune encephalitis, and evaluate the evidence behind the proposed pathophysiological mechanisms of autoantibodies in autoimmune encephalitis.

The gut microbiome - an essential role for human health

The complex and vast ecosystem of microorganisms within the gut, known as the gut microbiome, plays an important role in regulating numerous biological systematics. From immune system function and metabolism to brain health and enteric nervous system regulation, dysbiosis or changes in its composition can have significant impacts on human wellbeing such as autoimmune diseases, metabolic disorders, neurological and psychiatric disorders, and enteric neuropathies. Fortunately, research has uncovered the potential for targeting and manipulating the gut microbiome as a strategy in managing a wide variety of human ailments. By focusing on promoting a healthy balance within the guts microbial community, experts believe that theoretically curative treatments could arise related to the reduction/prevention of many diverse conditions which affect overall health. Through advances in understanding this crucial mechanism, we may be able to develop more effective therapies to promote optimal human health. As genetic sequencing technology continues expanding our knowledge in the field, future breakthroughs await those who patiently continue studying the fascinating world of the gut microbiome.