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B cells represent a relatively minor cell population within both the healthy and diseased central nervous system (CNS), yet they can have profound effects. This is emphasized in multiple sclerosis, in which B cell-depleting therapies are arguably the most efficacious treatment for the condition. In this Review, we discuss how B cells enter and persist in the CNS and how, in many neurological conditions, B cells concentrate within CNS barriers but are rarely found in the parenchyma. We highlight how B cells can contribute to CNS pathology through antibody secretion, antigen presentation and secretion of neurotoxic molecules, using examples from CNS tumours, CNS infections and autoimmune conditions such as neuromyelitis optica and, in particular, multiple sclerosis. Overall, understanding common and divergent principles of B cell accumulation and their effects within the CNS could offer new insights into treating these devastating neurological conditions., (© 2021. Springer Nature Limited.)

Background and Purpose: The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis., Methods: PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test., Results: The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02)., Conclusion: The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment., Systematic Review Registration: inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Sun, Zhou, Zhang, Xu, Cao and Fan.)

Natural killer (NK) cells, a major component of the innate immune system, have prominent immunoregulatory, antitumor proliferation, and antiviral activities. NK cells act as a double-edged sword with therapeutic potential in neurological autoimmunity. Emerging evidence has identified NK cells are involved in the development and progression of neuroimmunological diseases such as multiple sclerosis, neuromyelitis optica spectrum disorders, autoimmune encephalitis, Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, and idiopathic inflammatory myopathy. However, the regulatory mechanisms and functional roles of NK cells are highly variable in different clinical states of neuroimmunological diseases and need to be further determined. In this review, we summarize the evidence for the heterogenic involvement of NK cells in the above conditions. Further, we describe cutting-edge NK-cell-based immunotherapy for neuroimmunological diseases in preclinical and clinical development and highlight challenges that must be overcome to fully realize the therapeutic potential of NK cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Intermittent fasting, which includes periods of fasting and nutrition, has been considered a dietary approach for weight loss and metabolic health improvement. However, its potential benefits in autoimmune diseases have not been widely studied. This study aims to review the existing studies on the role and effects of intermittent fasting on autoimmune diseases. A comprehensive search was conducted on electronic databases such as PubMed, Scopus, Embase, and Web of Science, and relevant studies were included based on inclusion criteria. Studies show that intermittent fasting may have beneficial effects on various autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus, by reducing inflammatory markers, modulating the immune system, altering and improving gut microbiota, and enhancing cellular repair mechanisms through autophagy. However, evidence regarding the effects of intermittent fasting on other autoimmune diseases such as multiple sclerosis, systemic lupus erythematosus, thyroid diseases, and psoriasis is limited and inconclusive. Nevertheless, further research is needed to determine optimal intermittent fasting guidelines and its long-term effects on autoimmune diseases. Overall, this literature review proves intermittent fasting may be a promising dietary intervention for managing autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is an autoimmune, demyelinating disease with the highest incidence in women of childbearing age. The effect of pregnancy on disease activity and progression is a primary concern for women with MS and their clinical teams. It is well established that inflammatory disease activity is naturally suppressed during pregnancy, followed by an increase postpartum. However, the long-term effect of pregnancy on disease progression is less understood. Having had a pregnancy before MS onset has been associated with an older age at first demyelinating event, an average delay of 3.4 years. After MS onset, there is conflicting evidence about the impact of pregnancy on long-term outcomes. The study with the longest follow-up to date showed that pregnancy was associated with a 0.36-point lower disability score after 10-years of disease in 1830 women. Understanding the biological mechanism by which pregnancy induces long-term beneficial effects on MS outcomes could provide mechanistic insights into the elusive determinants of secondary progression. Here, we review potential biological processes underlying this effect, including evidence that acute sex hormone exposure induces lasting changes to neurobiological and DNA methylation patterns, and how sustained methylation changes in immune cells can alter immune composition and function long-term., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Chronic periodontitis (CP) is a multifactorial, chronic inflammatory disease of microbial etiology that manifests as a result of the dysfunction of the immune mechanism, culminating in the destruction of the alveolar bone of the jaws. Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system (CNS), leads to demyelination and degeneration of nerve axons and often causes severe physical and/or cognitive impairment. As CP and MS involve inflammatory mechanisms and immune dysfunction, researchers have attempted to study the association between them., Aim: To systematically review the literature on the epidemiological association between CP and MS in adults., Methods: PRISMA 2020 statement was used in the study protocol. The design was done according to the Cochrane methodology. A comprehensive literature search was performed in PubMed, Scopus and Cochrane databases; a manual search and evaluation of the gray literature was also performed. The meta-analysis was performed by Review Manager (RevMan) 5.4. Odds ratio (OR) with 95% confidence interval (CI) was defined as the effect size of the outcome. Heterogeneity was assessed by Chi-square and I 2 . The articles evaluated were written in English, without a time limit, concern observational studies (patient-controls) and report the diagnostic criteria of the diseases. Duplicate entries were excluded. To evaluate the reliability of the results of each study, Newcastle-Ottawa Scale (NOS) and GRADE tools were used. Two independent reviewers did all evaluations with a resolution of discrepancies by a third., Results: Meta-analysis included three observation studies examined 3376 people. MS patients are significantly more likely to be diagnosed with CP than healthy controls (OR 1.93, 95% CI 1.54-2.42, p<0.0001)., Conclusion: A high prevalence of CP was found among MS patients compared with healthy controls. Healthcare professionals should be aware of the association between these pathological entities to provide patients with high-quality care through an effective and holistic diagnostic and therapeutic approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Substantial links between autoimmune diseases have been shown by an increasing number of studies, and one hypothesis for this comorbidity is that there is a common genetic cause., Methods: In this paper, a large-scale cross-trait Genome-wide Association Studies (GWAS) was conducted to investigate the genetic overlap among rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 1 diabetes., Results and Discussion: Through the local genetic correlation analysis, 2 regions with locally significant genetic associations between rheumatoid arthritis and multiple sclerosis, and 4 regions with locally significant genetic associations between rheumatoid arthritis and type 1 diabetes were discovered. By cross-trait meta-analysis, 58 independent loci associated with rheumatoid arthritis and multiple sclerosis, 86 independent loci associated with rheumatoid arthritis and inflammatory bowel disease, and 107 independent loci associated with rheumatoid arthritis and type 1 diabetes were identified with genome-wide significance. In addition, 82 common risk genes were found through genetic identification. Based on gene set enrichment analysis, it was found that shared genes are enriched in exposed dermal system, calf, musculoskeletal, subcutaneous fat, thyroid and other tissues, and are also significantly enriched in 35 biological pathways. To verify the association between diseases, Mendelian randomized analysis was performed, which shows possible causal associations between rheumatoid arthritis and multiple sclerosis, and between rheumatoid arthritis and type 1 diabetes. The common genetic structure of rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 1 diabetes was explored by these studies, and it is believed that this important discovery will lead to new ideas for clinical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wen and Yu.)

Antigen-specific therapies allow for modulation of the immune system in a disease relevant context without systemic immune suppression. These therapies are especially valuable in autoimmune diseases such as multiple sclerosis (MS), where autoreactive T cells destroy myelin sheath. This work shows that an antigen-specific dual-sized microparticle (dMP) system can effectively halt and reverse disease progression in a mouse model of MS. Current MS treatments leave patients immunocompromised, but the dMP formulation spares the immune system as mice can successfully clear a Listeria Monocytogenes infection. Furthermore, we highlight design principles for particle based immunotherapies including the importance of delivering factors specific for immune cell recruitment (GM-CSF or SDF-1), differentiation (GM-CSF or FLT3L) and suppression (TGF-β or VD3) in conjunction with disease relevant antigen, as the entire formulation is required for maximum efficacy. Lastly, the dMP scheme relies on formulating phagocytosable and non-phagocytosable MP sizes to direct payload to target either cell surface receptors or intracellular targets, as the reverse sized dMP formulation failed to reverse paralysis. We also challenge the design principles of the dMP system showing that the size of the MPs impact efficacy and that GM-CSF plays two distinct roles and that both of these must be replaced to match the primary effect of the dMP system. Overall, this work shows the versatile nature of the dMP system and expands the knowledge in particle science by emphasizing design tenets to guide the next generation of particle based immunotherapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Multiple sclerosis (MS) is considered as an inflammatory autoimmune disease of the central nervous system (CNS), with a complex and heterogenic etiology. However, the involvement of inflammation in its pathophysiology is well documented and current therapies for MS are mainly immunosuppressive drugs. Although the available drugs reduce new lesions and relapses, their long-term outcome is not completely satisfactory. Inflammasomes are multimeric protein complexes that play a critical role in the inflammatory process. Several lines of evidence suggest an association between inflammasome activation and MS. In this paper, we have reviewed current studies that demonstrate the involvement of inflammasomes in MS development, in both animal model and MS patients. Furthermore, prior studies about the effect of inflammasome inhibitor drugs on development and progression of MS are discussed.

Immunosenescence, the gradual deterioration of immune function with age, holds profound implications for our understanding and management of multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system. Traditionally diagnosed in young adults, advancements in disease-modifying therapies and increased life expectancy have led to a growing number of older individuals with MS. This demographic shift underscores the need for a deeper investigation into how age-related alterations in immune function shape the course of MS, influencing disease progression, treatment effectiveness, and overall patient outcomes. Age-related immunosenescence involves changes such as shifts in cytokine profiles, the accumulation of senescent immune cells, and compromised immune surveillance, collectively contributing to a state known as "inflammaging". In the context of MS, these immunological changes disturb the intricate balance between inflammatory and regulatory responses, thereby impacting mechanisms of central immune tolerance and peripheral regulation. This paper stands out by combining the most recent advancements in immunosenescence with both pathophysiological and treatment perspectives on multiple sclerosis, offering a cohesive and accessible discussion that bridges theory and practice, while also introducing novel insights into underexplored concepts such as therapy discontinuation and the latest senolytic, neuroprotective, and remyelination therapies. Enhancing our understanding of these complexities will guide tailored approaches to MS management, ultimately improving clinical outcomes for affected individuals. [ABSTRACT FROM AUTHOR]

There are currently more than 80 different autoimmune diseases, affecting approximately 100 million people worldwide. The etiology of most autoimmune diseases is unknown. The highest incidence of these diseases is in the developed countries and they are more common in women than in men. Among the most often listed factors responsible for the onset of autoimmunity are genetic predisposition and the phenomenon known as molecular mimicry. The latter stems from a similarity between microbial antigens and antigens present in the human body (self antigens). It is believed that such homology is responsible for the production of auto-antibodies and in consequence attack of the immune system against host tissues and organs. However, the main molecular factors responsible for these diseases in most cases remain unknown. While pathogenesis of many autoimmune diseases indicates the presence of molecular mimicry, at the same time the similarities between the own and foreign structures do not always result in autoimmunity. Therefore, prediction of such crucial homology responsible for the development of autoimmune disease is extremely difficult. In this paper we present examples of autoimmune diseases such as type 1 diabetes, multiple sclerosis, reactive arthritis and the potential contribution of micro-organisms to the mechanism of molecular mimicry.

Multiple sclerosis (MS) is traditionally considered an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) with much knowledge available to support this view. However, this characterization implies that the primary event is an aberrant immune response directed at CNS antigens, promoting inflammation and later driving progressive axo-glial degeneration. Trials with potent anti-inflammatory agents and detailed neuropathological studies raise questions about this sequence of events. This hypothetical paper argues that MS may be primarily a "cytodegenerative" disease, possibly first involving the oligodendrocyte/myelin unit. Liberation of autoantigens secondarily recruits an immune response, the force of which heavily depends on the host's immune predisposition. Thus, the spectrum of MS from highly aggressive Marburg type, to primary progressive disease with little inflammatory burden, is governed by a "convolution" between the underlying cytodegeneration and the host's immune predilection. Clinical heterogeneity may be a reflection of a variable immune response, whereas in reality, the "real MS" may be a homogeneous degenerative process analogous to well known primary neurodegenerative diseases.

Lipids comprise over 70% of the myelin sheath but have been largely underinvestigated as autoantigens in multiple sclerosis (MS). This paper cites evidence for the involvement of lipid autoreactivity in MS and details how self lipid cross-reactivity may also contribute to the development of type 1 diabetes and autoimmune thyroid disorders (both of which have been associated with MS). A further analysis of myelin chemistry suggests several mechanisms by which infection may contribute to etiology and trigger lipid autoreactivity via molecular mimicry. This analysis may aid the development of new therapies for autoimmune diseases., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

The majority of autoimmune disorders are characterized by female predominance. Several mechanisms have been proposed as explanations for this gender bias, among them X chromosome inactivation. An increased frequency of skewed X inactivation has been found in some autoimmune disorders, like scleroderma and autoimmune thyroid disease, and may thus offer a possible explanation for the female predominance. Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, with pathological features of an autoimmune disorder. The incidence of MS in females is approximately twofold compared to the incidence in males. X inactivation does not seem to be part of the explanation for the gender bias in MS. This paper reviews the possible role of X chromosome inactivation in some autoimmune diseases, and describes a recent study of X inactivation in females with MS.

Complex neuroendocrine mechanisms regulating the immune response can be recognized in all autoimmune diseases. Such mechanisms develop through endocrine loops and feedback processes along the hypothalamus-pituitary-gonads axis and the hypothalamus-pituitary- adrenal gland axis. Females are not only more susceptible to autoimmune diseases, but are also more exposed to relevant variations of hormonal levels that physiologically go along with women's life. This paper reviews female-specific issues in multiple sclerosis and how treatments must be considered accordingly. In particular, aspects related to puberty, menses, fertility, pregnancy, lactation and menopause are considered in addition to epidemiological and clinical issues.

Purpose of Review: Autoimmune neurologic diseases are being increasingly recognized, and treated with conventional immunosuppressive agents. Patients with 'refractory' conditions have been treated with high-dose therapy, with or without autologous stem cell transplants. This paper reviews the rationale, methods, and recent results of high-dose therapy and the questions that it raises., Recent Findings: High-dose therapy has been used in progressive multiple sclerosis and in myasthenia gravis and autoimmune neuropathies that are refractory to conventional immunotherapy. A variety of methods of immune ablation have been used; most require hematopoietic 'rescue' with stem cell transplantation. High-dose cyclophosphamide alone is immunoablative but not myeloablative, permitting the patient's endogenous stem cells to repopulate the hematopoietic/immune systems. The results have been highly encouraging in many but not all cases, with durable responses in the limited time they have been followed up. The treatments carry some risks and have been reserved for refractory cases until now., Summary: High-dose therapy, without or with stem cell transplantation, is a valuable resource for the treatment of patients with refractory autoimmune neurologic diseases. It is important to define the diseases and patient characteristics likely to lead to benefit, to optimize the methods of treatment and to establish when in the patient's course to administer it. High-dose therapy may eventually become the standard for treatment of severe progressive autoimmune neurologic disorders.

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. [ABSTRACT FROM AUTHOR]

Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A 'disease in a dish' can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, '-omics' analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells. [ABSTRACT FROM AUTHOR]

Controversy remains as to the efficacy, route of administration and dose of glucocorticosteroid (GCS) in multiple sclerosis (MS) therapy. With the recent approval of new disease modifying treatments and increasing interest in cost-benefit assessments, it is timely to critically consider their role in MS therapeutics. In this paper we review our current understanding of the cellular and molecular mechanisms of action of GCS as they relate to the postulated pathophysiology of MS. We also critically review the use of glucocorticosteroid therapy to: (1) improve recovery from exacerbations of MS, (2) delay the onset of MS in patients who experience a first episode of monosymptomatic optic neuritis, and (3) delay the time to onset of sustained progression of disability in patients with clinically definite MS.

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Although the cause(s) of multiple sclerosis is not known, an immunological process is considered to be a significant element in the pathogenesis of the disease. The paper describes important immunological features in multiple sclerosis and how immunological mechanisms can mediate demyelination.

Background and purpose: The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis. Methods: PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test. Results: The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02). Conclusion: The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation. B-cell depleting therapies have shown success as disease-modifying treatments (DMTs) in MS, highlighting the potential of BTK inhibitors for this indication; however, first-generation BTK inhibitors exhibit a challenging safety profile that is unsuitable for chronic use, as required for MS DMTs. A second generation of highly selective BTK inhibitors has shown efficacy in modulating MS-relevant mechanisms of pathogenesis in preclinical as well as clinical studies. Six of these BTK inhibitors are undergoing clinical development for MS, three of which are also under investigation for chronic spontaneous urticaria (CSU), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase II trials of selected BTK inhibitors for MS showed reductions in new gadolinium-enhancing lesions on magnetic resonance imaging scans; however, the safety profile is yet to be ascertained in chronic use. Understanding of the safety profile is developing by combining safety insights from the ongoing phase II and III trials of second-generation BTK inhibitors for MS, CSU, RA and SLE. This narrative review investigates the potential of BTK inhibitors as an MS DMT, the improved selectivity of second-generation inhibitors, comparative safety insights established thus far through clinical development programmes and proposed implications in female reproductive health and in long-term administration. Plain language summary: A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis Why was this study done? This study was done to find out about current knowledge on a type of drug, called Bruton's tyrosine kinase inhibitors, or BTK inhibitors. There are currently six BTK inhibitors being studied as a possible new drug for treating multiple sclerosis (MS). Some of these six drugs are also being studied as a possible new drug for chronic spontaneous urticaria, rheumatoid arthritis and systemic lupus erythematosus. These are all autoimmune conditions, where the immune system mistakenly attacks parts of the body. Clinician scientists wanted to understand what is currently known about BTK inhibitors, how they work in the laboratory and how safe they could be for treating autoimmune conditions. This could help us understand more about BTK inhibitors in MS. What did the scientists do? The scientists assessed existing research on these six BTK inhibitors, through a process known as a literature review. These were results from ongoing clinical trials, and information collected through studying BTK inhibitors in laboratories. The researchers pieced together all these findings, to produce this paper that summarizes the results. What did the scientists find? The scientists found that most studies of BTK inhibitors for MS are still ongoing. So far, BTK inhibitors seem to show reasonable safety in most studies, but it is too early to know. The researchers also found out about how BTK inhibitors work in the lab, about what could happen if the drugs are taken for a long time and how they could impact female reproductive health. What do these findings mean? These findings will help other scientists learn more about BTK inhibitors in MS. Trials with BTK inhibitors for MS are still ongoing, but piecing together all the current findings gives a picture of what we know and what still needs to be done. [ABSTRACT FROM AUTHOR]

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This article, titled "Editorial: Comorbidity in multiple sclerosis and related disorders," discusses the co-occurrence of multiple physical or psychological health conditions in individuals with multiple sclerosis (MS) and related disorders. The article highlights the increased vulnerability of MS patients to developing comorbidities and explores the various factors that contribute to this co-occurrence, such as direct causation, common risk factors, and the impact of disease-modifying therapies. The article also mentions the adverse health outcomes, increased medical costs, and decreased quality of life associated with comorbidities in MS patients. The research topic includes eight papers that investigate the patterns and effects of comorbidities in demyelinating disorders, as well as the impact of treatments on MS outcomes. [Extracted from the article]

The author presents evidence from published papers of research done by numerous investigators that Multiple, Sclerosis (MS) is an autoimmune disease, that the target tissue is the myelin sheath which covers the nerve fibers in the brain and spinal cord, that Myelin Basic Protein (MBP) is the antigen or one of the antigens involved, that the autoimmune reaction is effected by sensitized lymphocytes together with a specific antibody, that Experimental Allergic Encephalomyelitis (EAE) produced in animals can be used as a model for MS, and that the autoimmune reaction in MS can possibly be suppressed by the use of MBP given by an intravenous procedure together with an immunosuppressive drug and a corticosteroid.

Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto-immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses.

Multiple sclerosis (MS) is an autoimmune disease for which it is difficult to find exact disease-related genes. Effectively identifying disease-related genes would contribute to improving the treatment and diagnosis of multiple sclerosis. Current methods for identifying disease-related genes mainly focus on the hypothesis of guilt-by-association and pay little attention to the global topological information of the whole protein-protein-interaction (PPI) network. Besides, network representation learning (NRL) has attracted a huge amount of attention in the area of network analysis because of its promising performance in node representation and many downstream tasks. In this paper, we try to introduce NRL into the task of disease-related gene prediction and propose a novel framework for identifying the disease-related genes multiple sclerosis. The proposed framework contains three main steps: capturing the topological structure of the PPI network using NRL-based methods, encoding learned features into low-dimensional space using a stacked autoencoder, and training a support vector machine (SVM) classifier to predict disease-related genes. Compared with three state-of-the-art algorithms, our proposed framework shows superior performance on the task of predicting disease-related genes of multiple sclerosis. [ABSTRACT FROM AUTHOR]

Epidemiological data suggest that the prevalence of autoimmune diseases is increasing. Although evidence implies that people with chronic illnesses experience higher levels of burnout, there are few available insights for developing preventative interventions. This paper builds on the conservation of resources (COR) and the job demands–resources (JD‐R) framework to investigate the association between impaired health, burnout, and work engagement. In two studies, we research the role of health status as a resource, respectively, autoimmune illness symptom severity as a diminished resource, and investigate its variance explanation in burnout and work engagement above and beyond the effects of job demands and resources. Study 1 investigated the hypotheses among 87 employees with inflammatory bowel diseases. Controlling for job demands and resources, symptom severity was positively associated with (exhaustion) burnout and negatively associated with work engagement. In Study 2, we applied mixed model analyses using a sample of 129 employees with multiple sclerosis. We found significant associations of symptom severity on burnout and vigor work engagement above and beyond the effects of job demands and social support. Our studies provide important insights for employees with chronic illnesses and the organizations in which they work and give indications for theory development, future research, and the development of interventions. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is the branch of science aiming at creating algorithms able to carry out tasks that typically require human intelligence. In medicine, there has been a tremendous increase in AI applications thanks to increasingly powerful computers and the emergence of big data repositories. Multiple sclerosis (MS) is a chronic autoimmune condition affecting the central nervous system with a complex pathogenesis, a challenging diagnostic process strongly relying on magnetic resonance imaging (MRI) and a high and largely unexplained variability across patients. Therefore, AI applications in MS have the great potential of helping us better support the diagnosis, find markers for prognosis to eventually design more powerful randomised clinical trials and improve patient management in clinical practice and eventually understand the mechanisms of the disease. This topical review aims to summarise the recent advances in AI applied to MRI data in MS to illustrate its achievements, limitations and future directions. [ABSTRACT FROM AUTHOR]

The author discusses the capability of cytidine-5'- diphospho-choline (CDP) to enhance remyelination in two demyelinating disease animal models that suppressed auto-immune inflammatory disease activity in multiple sclerosis (MS). He outlines that CDP-choline ameliorated experimental allergic encephalomyelitis (EAE) disease course in promoting remyelination. He also presents an analysis of yearly magnetic resonance imaging (MRI) scans by a Jacobian integration method.

The advent of CRISPR-Cas9 gene-editing technology has revolutionized the biomedical field, reshaping and elevating the possibilities in which medicine approaches diagnosis, treatment, prevention, and potentially curing certain diseases. The prospect of CRISPR-Cas9 gene-editing has transformed the seemingly abstract hypothetical into practical solutions that have the scope to possibly cure an extensive range of currently "incurable" genetic diseases. This list includes Multiple Sclerosis (MS), a debilitating and chronic autoimmune disorder that causes rapid neurodegeneration in the central nervous system. Although the etiological cause of MS remains unknown, CRISPR-Cas9 has the potential to effectively ameliorate its clinical symptoms by acting on several molecular factors that result in the progression of the disease. When attempting to achieve successful genome editing, several factors need to be taken into consideration. This paper highlights the importance of different stages involved in the gene- editing process, including components of CRISPR -- Cas9 technology, effective expression and delivery methods, novel approaches to treat MS, as well as the ethical aspects surrounding the therapeutic use of gene-editing to cure and treat an extensive range of diseases including MS. [ABSTRACT FROM AUTHOR]

One the disease modifying therapies (DMTs) that has been reported to be beneficial in multiple sclerosis (MS) is ponesimod, and as it holds true for all other autoimmune diseases, attempts to design immunosuppressive agents to help control the progression of MS while causing minimal side effects play a pivotal role in helping individuals suffering from the disease. Consequently, we have designed this review to comprehensively look into the safety and efficacy of ponesimod in persons with MS. A systematic database search was performed in March 2021. Double‐blinded RCTs on patients with MS with Ponesimod as their experimental medication were included. Annualized relapse rate (ARR), disability accumulation rate (DAR), the score of Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ–RMS), and adverse reactions were interpreted as efficacy and safety measurements, respectively. Ninety‐Five papers were retrieved in the literature search. After duplicate elimination, 92 studies remained. Finally, the review included two studies that met the criteria and used varied study designs. Ponesimod reduced ARR by 30.5% (p value = 0.001), DRA by 58% (p value = 0.29), and FSIQ‐RMS mean score by 3.57 (p value = 0.002). Meanwhile, the drugs have few side effects which were mild or moderate in intensity but has less cardiovascular side effects comparing to other S1P drugs like fingolimod. The advantageous properties of ponesimod in terms of its favorable risk: benefit and convenience profile, ponesimod has been regarded recently as a potential SIP‐1 drug for treating MS. [ABSTRACT FROM AUTHOR]

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Evidence of the effectiveness of B-cell-depleting monoclonal antibodies (mAbs) in multiple sclerosis (MS) prompted a partial revisitation of the pathogenetic paradigm of the disease, which was, so far, considered a T-cell-mediated autoimmune disorder. Mechanisms underlying the efficacy of B-cell-depleting mAbs in MS are still unknown. However, they likely involve the impairment of pleiotropic B-cell functions different from antibody secretion, such as their role as antigen-presenting cells during both the primary immune response in the periphery and the secondary response within the central nervous system (CNS). A potential impact of B-cell-depleting mAbs on inflammation compartmentalised within the CNS was also suggested, but little is known about the mechanism underlying this latter phenomenon as no definite evidence was provided so far on the ability of mAbs to cross the blood–brain barrier and reliable biomarkers of compartmentalised inflammation are lacking. The present paper briefly summarises the immunopathogenesis of MS with a focus on onset of autoimmunity and compartmentalisation of the immune response; mechanisms mediating B-cell depletion and underlying the effectiveness of B-cell-depleting mAbs are also discussed. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are chronic, multifactorial conditions. Through machine learning (ML), a branch of the wider field of artificial intelligence, it is possible to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management. Here, we surveyed the use of ML methods to address clinical problems in autoimmune disease. A systematic review was conducted using MEDLINE, embase and computers and applied sciences complete databases. Relevant papers included "machine learning" or "artificial intelligence" and the autoimmune diseases search term(s) in their title, abstract or key words. Exclusion criteria: studies not written in English, no real human patient data included, publication prior to 2001, studies that were not peer reviewed, non-autoimmune disease comorbidity research and review papers. 169 (of 702) studies met the criteria for inclusion. Support vector machines and random forests were the most popular ML methods used. ML models using data on multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease were most common. A small proportion of studies (7.7% or 13/169) combined different data types in the modelling process. Cross-validation, combined with a separate testing set for more robust model evaluation occurred in 8.3% of papers (14/169). The field may benefit from adopting a best practice of validation, cross-validation and independent testing of ML models. Many models achieved good predictive results in simple scenarios (e.g. classification of cases and controls). Progression to more complex predictive models may be achievable in future through integration of multiple data types. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2011; 41 (11): 1254-1258 Abstract Background Research using experimental autoimmune encephalitis (EAE) models accounts for almost 20% of the papers. published in multiple sclerosis (MS). Methods We performed a literature review of papers indexed with ISI Web of Science on EAE and MS over the last 30 years and a detailed analysis of studies of molecular pathways in EAE published in 2008 and 2009. Results The impact of EAE studies declines more rapidly than other studies published on MS (EAE cited corrected half-life = 4·00 years vs. MS cited corrected half-life = 9·66 years, P < 0·0001). The pathology of EAE differs quite markedly from that observed in the human disease. EAE has implicated many different genes as important to pathogenesis but only a minority of these are supported by human studies. Conclusions Future research should critically appraise precisely what is being modelled by EAE before drawing conclusions about human disease. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA) are common, chronic, autoimmune diseases affecting many people worldwide. While clinically very different in their phenotype, both diseases are thought to have an autoimmune-mediated origin. MS and RA share genetic similarities, and in both diseases, antibodies against host antigens can be found. Aside from the well-known somatic symptoms, many RA patients also show signs and symptoms of psychiatric illnesses, of which depression is the most common diagnosis. In this commentary, both diseases will be introduced and briefly characterized individually and then compared. Depression will be introduced as one of the most frequent psychiatric diseases in the general population. This paper focuses on presenting the possible causes, including psychosocial factors, genetics, and immunologic mechanisms. Hypotheses aimed to explain the higher incidence of depression in these two seemingly different autoimmune diseases will be discussed. [ABSTRACT FROM AUTHOR]

Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy. [ABSTRACT FROM AUTHOR]