Immunophenotyping of Cerebrospinal Fluid Cells in Multiple Sclerosis

Alvermann, Sascha; Hennig, Christian; Stüve, Olaf; Wiendl, Heinz; Stangel, Martin

doi:10.1001/jamaneurol.2014.395

Cited by 57 publications

(36 citation statements)

References 44 publications

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“…NTZ‐treated MS patients show significantly reduced counts of both CD4 + and CD8 + T‐cell subsets in their CSF , arguing that NTZ blocks CNS entry of both CD4 + and CD8 + T‐cell subsets and that reducing the CSF pool of T cells interferes with CNS immunosurveillance. The increased risk for PML observed under NTZ therapy has supported this notion; however, it completely fails to explain how reduced CNS immune surveillance will establish a specific risk for infection to one single virus.…”

Section: Discussionmentioning

confidence: 99%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults. When MS is not treated, it leads to irreversible and severe disability. The etiology of MS and its pathogenesis are not fully understood. The recent discovery that MS-associated genetic variants code for molecules related to the function of specific immune cell subsets is consistent with the concept of MS as a prototypic, Tcell-mediated autoimmune disease targeting the CNS. While the therapeutic efficacy of the currently available immunomodulatory therapies further strengthen this concept, differences observed in responses to MS treatment as well as additional clinical and imagingobservations have also shown that the autoimmune pathogenesis underlying MS is much more complex than previously thought. There is therefore an unmet need for continued detailed phenotypic and functional analysis of disease-relevant adaptive immune cells and tissues directly derived from MS patients to unravel the immune etiology of MS in its entire complexity. In this review, we will discuss the currently available MS treatment options and approved drugs, including how they have contributed to the understanding of the immune pathology of this autoimmune disease.Keywords: Autoantibodies r Autoimmune pathogenesis r Autoimmunity r Autoreactive B cells r Autoreactive T cells r Experimental autoimmune encephalomyelitis r Multiple sclerosis r Treatment Introduction-MS as an autoimmune diseaseMS is considered a prototypic organ-specific autoimmune disease targeting the CNS with inflammatory lesions, demyelination, axonal/neuronal damage, and metabolic changes [1,2]. Relapsing-remitting and secondary progressive MS (RRMS, SPMS) are the two most frequent forms of MS, which often affect young adults between 20 and 40 years of age, and women three times more often than men [3]. Typical clinical signs include temporary loss of vision, sensory and motor problems, but also fatigue, neurocognitive changes, and impairment of bladder, bowel, and Correspondence: Britta Engelhardt ; Roland Martin e-mail: bengel@tki.unibe.ch; roland.martin@usz.ch sexual functions. During the relapsing-remitting phase neurological deficits, which occur in bouts and may last from days to a few weeks, usually disappear again, but after several years, disability gradually builds up. Depending on the individual course this secondary progressive disease with continuously increasing disability may never set in, but often starts after 15-20 years of RRMS. In a small percentage of patients such a progressive course is seen from the beginning, which is referred to as primary progressive MS (PPMS) and seen in females and males with equal frequency [3].Evidence for an autoimmune pathogenesis of MS was shown in its animal model, experimental autoimmune encephalomyelitis (EAE) (summarized in [4,5] Treatments of MSAs already noted above, the various treatments of MS deserve particular mentioning not only because they have changed clinical practice and can be considered ...

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Section: Discussionmentioning

confidence: 99%

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

et al. 2016

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“…Increased numbers of T cells and B cells are found in the CSF of patients with CNS infections or multiple sclerosis [3,16].…”

Section: Neuroimmune Function Of the Choroid Plexuses In Neurologicalmentioning

confidence: 99%

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

et al. 2018

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The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

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“…In healthy individuals, it is mostly central memory T cells and B cells and low numbers of innate immune cells that are detected in the CSF [7, 46, 71, 111]. This further underscores the ability of activated T and B cells to breach the outer brain barriers in the absence of neuroinflammation and perform immunosurveillance of the CNS by entering the CSF spaces.…”

Section: Efferent Pathways Between Lymph Nodes and The Cnsmentioning

confidence: 99%

Vascular, glial, and lymphatic immune gateways of the central nervous system

et al. 2016

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Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood–brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer’s disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

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Immunophenotyping of Cerebrospinal Fluid Cells in Multiple Sclerosis

Cited by 57 publications

References 44 publications

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Vascular, glial, and lymphatic immune gateways of the central nervous system

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