Immunology Of Multiple Sclerosis Research Articles

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.

The immunology of multiple sclerosis.

Our incomplete understanding of the causes and pathways involved in the onset and progression of multiple sclerosis (MS) limits our ability to effectively treat this complex neurological disease. Recent studies explore the role of immune cells at different stages of MS and how they interact with cells of the central nervous system (CNS). The findings presented here begin to question the exclusivity of an antigen-specific cause and highlight how seemingly distinct immune cell types can share common functions that drive disease. Innovative techniques further expose new disease-associated immune cell populations and reinforce how environmental context is critical to their phenotype and subsequent role in disease. Importantly, the differentiation of immune cells into a pathogenic state is potentially reversible through therapeutic manipulation. As such, understanding the mechanisms that provide plasticity to causal cell types is likely key to uncoupling these disease processes and may identify novel therapeutic targets that replace the need for cell ablation.

New concepts on immunology of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory and immune-driven demyelinating disease of the central nervous system (CNS). During the past decade, major advances have been made to understand the development of MS as well as its progressive stage.Here, we discuss some emerging concepts on immunology of MS, including the growing interest in the involvement of gut microbiota and the recent pathological concepts on the progression phase. Finally, we present some immuno-tools recently available that contribute to better understand diversity and function of the immune system.

Immunology of Multiple Sclerosis.

Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the central nervous system (CNS). A complex genetic background with the HLA-DR15 haplotype as the main genetic risk factor and over 100 mostly immune-related minor risk alleles as well as several environmental factors contribute to the etiology of MS. With respect to pathomechanisms, autoimmune inflammation in early MS is primarily mediated by adaptive immune responses and involves autoreactive T cells, B cells, and antibodies, while the later, chronic stages of MS are characterized by a compartmentalized immune response in the CNS with activated microglia and macrophages. A host of immune cells and mediators can contribute to the autoimmune process, but CNS-related factors such as localization of lesions, vulnerability of oligodendrocytes, neurons/axons, and secondary metabolic changes all play a role in the heterogeneous expression of the disease, including different pathologic lesion patterns, neuroimaging findings, disease courses, and severity and response to treatment.

Immunology of MS

Multiple sclerosis is an autoimmune disease affecting central nervous system myelin. Myelin antigen specific auto-reactive cells are activated in the periphery then migrate to the central nervous system where they initiate an inflammatory response. The demyelinating process in multiple sclerosis (MS) involves T-cells, immunoglobulins and complement. Remyelination occurs to some extent but several factors contribute to the failure of remyelination. Understanding the immunopathogenesis of MS helps in designing new therapies and in understanding the mechanisms and potential side effects of existing drugs. Multiple sclerosis is an autoimmune disease affecting central nervous system myelin. Myelin antigen specific auto-reactive cells are activated in the periphery then migrate to the central nervous system where they initiate an inflammatory response. The demyelinating process in multiple sclerosis (MS) involves T-cells, immunoglobulins and complement. Remyelination occurs to some extent but several factors contribute to the failure of remyelination. Understanding the immunopathogenesis of MS helps in designing new therapies and in understanding the mechanisms and potential side effects of existing drugs.

Biochemical Parameters Alterations in Multiple Sclerosis: A Longitudinal Study and Review of the Literature

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and is characterized by inflammation, demyelination and desctruction of oligodendrocytes and axons. The immunology of MS is complex, involving autoreactive Th1 and Th17 lymphocytes, cells of the innate immune system including dedritic, natural killer (NK) and microglia cells, as well as vascular endothelial cells. Multiple Sclerosis (MS) is based by a series of biochemical changes affecting to different extent neuronal functions; great attention has been focused on: liver enzymes, thyroid function tests, autoantibodies, lipid profile and uric acid levels. Following the introduction of therapy with drugs that modify the course of disease, more attention has been paid to the change of biochemical parameters, in particular to evaluate possible adverse effects. Aim of this study was to perform a review of the literature on biochemical alterations in treated and untreated MS patients and to assess laboratory parameters alterations in a cohort of MS patients, before and during treatment. On a total of 624 patients followed at our center, we selected those who practiced for the first time a therapy with IFN beta 1a at various doses, IFN beta 1b and Glatiramer acetate, that were 595 (95%), with baseline biochemical evaluation available in 488 (82%) (307 females, mean age 36.6 years). We considered the evolution of various biochemical parameters during treatment. The following outcome variables were evaluated: laboratory changes, in particular liver function, thyroid function, lipids and blood cell count. Percentages were compared using the chisquare test. ANOVA was performed to evaluate changes of laboratory tests over time between therapy groups. Our finding confirm the presence of biochemical alterations at baseline, in particular regarding liver enzymes, thyroid hormones and lipids. Treatment effects were more evident on liver enzymes elevation, anti thyroid antibodies production and blood cholesterol decrease. These effects were mainly transient and self remitting without suspension of therapy. Biochemical alterations, mainly related to autoimmune pathology and lipid metabolism change were encountered. Treatments increased transient biochemical alterations particulary in patients with baseline changes, suggesting a stricter monitoring of blood exams in this category of patients.

What are new therapies teaching us about the immunology of multiple sclerosis?

Michael K Racke† & Amy E Lovett-Racke †Author for correspondence The Ohio State University Medical Center, Department of Neurology and Molecular Virology, Immunology, and Medical Genetics, 1654 Upham Drive, 445 Means Hall, Columbus, OH 43210, USA Tel.: +1 614 293 4036 Fax: +1 614 293 9029 michael.racke@osumc.edu ‘Does the success of natalizumab imply that neutrophils play little or no role in most cases of relapsing–remitting multiple sclerosis?’

The Immunology of Multiple Sclerosis

Recent years have witnessed a remarkable growth in literature related to the biology and treatment of multiple sclerosis (MS). The focus of this article is on aspects of the human immune response that have been implicated in the MS disease process and, as a corollary, represent rational targets for the development of safe and effective therapies. Much of the thinking about immune pathophysiology in patients with MS has been shaped by studies in animal models of central nervous system (CNS) inflammation. Translation to the human disease has continued to pose challenges. A simplified model of MS immune pathophysiology is presented to illustrate the basic principles by which peripheral immune activation, as well as compartmentalized immune responses within the CNS, is likely to impact the disease process and to identify the putative sites of action of current and future MS treatments.

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by -meningeal lymphoid follicles with germinal centers.

Immunopathogenesis and immunotherapy of multiple sclerosis

Multiple sclerosis (MS) is a chronic disease of the CNS that is characterized by inflammation, demyelination and axonal injury. Although the etiology of MS is still unknown, many findings point toward a central role for the immune system in the pathogenesis of the disease. This hypothesis is strongly supported by the beneficial effects of immunomodulatory and immunosuppressive therapy on disease activity. Over the past few years, substantial progress has been made in deciphering the immune response in MS. Although animal models have advanced our knowledge of basic mechanisms of immune responses in the CNS, recent studies have also highlighted the differences between MS and its animal equivalent, experimental autoimmune encephalomyelitis. New immunotherapeutic agents have been developed and evaluated in clinical trials. Here, we review current knowledge of the immunopathogenesis of MS and corresponding animal models of disease, and discuss new immunointerventional treatment strategies based on changing pathogenetic concepts.

Interferon β in multiple sclerosis: is IL-12 suppression the key?

Recently, much has been learned about the immunology of multiple sclerosis (MS). However, a mechanistic understanding of currently employed immunomodulatory therapies has lagged behind, hindering both the search for more effective agents and clearer insight into the immunopathogenesis of MS. Christopher Karp and colleagues explore a unifying hypothesis for the mechanism of action of interferon β in MS: suppression of interleukin 12 production.

Recent advances in immunology in multiple sclerosis.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that is of possible autoimmune origin. This article is divided into three parts, reviewing recent advances in three selected topics regarding the immunology of multiple sclerosis. The first part addresses the consequences of T cell and oligodendrocyte death in the inflammatory lesions. The second covers the recent experimental evidence favouring the involvement of infectious agents in the pathophysiology of central nervous system autoimmune diseases. The third part concerns the mode of action of interferon-beta in multiple sclerosis. These new advances have lead to a better understanding of the immunopathology of multiple sclerosis and therefore open new therapeutic possibilities.

The Immunology of Multiple Sclerosis and its Animal Model, Experimental Allergic Encephalomyelitis

Two questions were posed at the beginning of this article. Is EAE a good model for MS? And, is MS an autoimmune disease? The first question is easier to address than the second. EAE is the best available model for the inflammatory processes that occur in MS, and for the disease process. The latter depends somewhat on study of chronic relapsing EAE, rather than early or mono-episodic EAE, which, although of great immunological interest, is of less relevance to the established disease that presents as MS. The second question asks whether MS fulfills Koch's postulates as an autoimmune disease. MS has all the hallmarks of an inflammatory disease of the CNS. The question then is whether the inflammation is autoimmune. The evidence presented shows a considerable autoimmune component to MS inflammation, raising the subsidiary question of whether autoimmune reactivity induces MS. This remains unanswerable for the present, and it should be kept in mind that the same question also would be unanswerable by observation of EAE. The major postulate therefore remains unfulfilled. Diagnosis of MS as an autoimmune disease requires definitive identification of the autoantigen; otherwise, the possibility remains open that this is a disease resulting from the inadvertent activation and dysregulation of immune processes in the CNS that, themselves, are not directed at that organ.

The immunology of multiple sclerosis: new intricacies and new insights.

New epidemiology and genetics data have supported the broad concept that multiple sclerosis represents an acquired autoimmunity, which is determined in part by inheritance. Furthermore, it is now widely believed that the pathogenesis of multiple sclerosis involves autoimmune reactivity that is directed against myelin proteins. Much of our understanding of myelin-directed autoimmunity has come from studies on experimental autoimmune encephalomyelitis, a T-cell-mediated, multiple sclerosis-like disease, which is provoked by immunizing animals with myelin proteins. During the past year, significant progress has been made in delineating immune reactivity to myelin antigens. Models that feature restricted epitope recognition and limited T-cell receptor gene utilization have been challenged (often by their original authors). Unifying new concepts include dynamic temporal diversification of the autoimmune response and clear-cut distinctions between the potential and engaged autoimmune repertoire. An abundance of new information about the biologic determinants of T-cell immunopathogenicity is leading rapidly to innovative therapeutic strategies.

A possible paradox in the immunology of multiple sclerosis: Its apparent lack of ‘specificity’ might provide clues to the etiology

As a further development from an earlier hypothesis (13), a pathogenic role of polyspecific natural, idiotypically connected antibodies is claimed, that recognize concomitantly a variety of CNS antigens and are matured to some degree to higher-affinity anti-CNS antibodies without ever losing their network association. On that basis, nitrophenol-carrier conjugates well-known to be foreign target antigens of natural antibodies and present in food commodities that have epidemiological links to MS, are considered as paradigmatic for agents of possible etiologic importance.

Immunology of multiple sclerosis.

Immunology of multiple sclerosis.

Immunology of Multiple Sclerosis

Evidence points to the conclusion that abnormal regulation of the immune response in MS contributes to ongoing immune activity.