Piet Mondrian’s trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011

Steinman, Lawrence; Axtell, Robert C.; Barbieri, Donald; Bhat, R.; Brownell, Sara E.; Jong, Brigit A. de; Dunn, Shannon; Grant, Jacqueline L; Han, May; Ho, Peggy P.; Kuipers, Hedwich F.; Kurnellas, Michael; Ousman, Shalina S.; Rothbard, Jonathan B.

doi:10.1177/1352458512470730

Cited by 8 publications

(4 citation statements)

References 54 publications

(97 reference statements)

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“…Whereas the role of Th1 cells is considered contributory in the pathogenesis, perhaps more so later in the disease, the current view on the role of Th cells in MS/EAE pathogenesis is characterized by the Th1/Th17 paradigm. Although the precise role of a Th1/Th17-mediated response in MS remains unclear, the discovery that αB-crystallin is produced in copious amounts in MS lesions suggests that it is a guardian molecule because it attenuates disease and downregulates the production of Th1 and Th17 pathways and binds these pro-inflammatory mediators in plasma [Fletcher et al 2010; Steinman et al 2013]. In this context a systemic humoral response to αB-crystallin correlates with disease activity and severity [Agius et al 1999].…”

Section: Immunobiology Of Acute Multiple Sclerosis Exacerbationsmentioning

confidence: 99%

Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis

Berkovich

Agius

2014

Ther Adv Neurol Disord

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Acute and subacute inflammation, the mechanisms by which demyelination and axonal loss occur in multiple sclerosis (MS), result from the migration of activated immune cells into the central nervous system parenchyma. The triggering antigen is unknown, but the process involves deregulated immune response of T and B lymphocytes, macrophages, and mediators with expansion of autoreactive T cells creating a shift in the balance of pro- and anti-inflammatory cytokines favoring inflammation. Ongoing disease activity and exacerbations early in the course of relapsing-remitting MS may prevent full remission and propagate future progressive disability. A key strategy of immune therapy is timely initiation of treatment to achieve remission, followed by maintenance of remission. In this context, treatment with high-dose methylprednisolone (MP) is currently recommended to induce a faster recovery from a clinical exacerbation that results from an acute inflammatory attack. Adrenocorticotropic hormone (ACTH or corticotropin) gel is an alternative for patients who do not respond to or do not tolerate corticosteroids. ACTH is a universal agonist in the melanocortin (MC) system and, as such, among other functions, stimulates the adrenal cortex to produce cortisol. MCs are a family of peptides that includes ACTH and other MC peptides. This system has five classes of receptors, all of which show a strong affinity for ACTH, suggesting a more complex and dynamic mechanism than only inducing endogenous corticosteroid production. ACTH and MCs regulate processes relevant to MS, including anti-inflammatory and immunomodulatory functions involving lymphocytes, macrophages, the sympathetic nervous system involved in inflammatory processes, and reduction of pro-inflammatory cytokines. The clinical implications of the mechanistic differences between corticosteroid and ACTH gel treatment remain to be elucidated. Recent data show that patients experiencing an acute exacerbation, who previously had suboptimal response to or were unable to tolerate MP treatment, showed positive clinical outcomes with fewer adverse events with ACTH gel.

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Section: Immunobiology Of Acute Multiple Sclerosis Exacerbationsmentioning

confidence: 99%

Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis

Berkovich

Agius

2014

Ther Adv Neurol Disord

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“…In a wonderful collaboration with Dr. Sohail Ahmed, then at Novartis Vaccines in Siena, Italy, we studied how a particular influenza vaccine in 2009 triggered narcolepsy in individuals who were HLA-DQ 0602 (a gene locus in HLA). The research showed that there is a component of the influenza virus that is contained in some are worth trying to answer (115). These individuals are among my most eloquent teachers and scientific colleagues.…”

Section: Discussionmentioning

confidence: 99%

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

Steinman

2016

Mol Med

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Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by Lawrence Steinman, MD, of Stanford University in California. A visionary in the field of neurology, this is the story of Dr. Steinman's scientific journey.

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“…It affects more than 2.5 million people worldwide and it is mainly diagnosed in young adults between 20 and 40 years [ 5 ]. MS is three times more prevalent in women than men, and there is evidence that this ratio may be increasing [ 6 , 7 ], a phenomenon shared with several other autoimmune diseases.…”

Section: Introductionmentioning

confidence: 99%

Profiling of Plasma Extracellular Vesicle Transcriptome Reveals That circRNAs Are Prevalent and Differ between Multiple Sclerosis Patients and Healthy Controls

et al. 2021

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(1) Background: Extracellular vesicles (EVs) are released by most cell types and are implicated in several biological and pathological processes, including multiple sclerosis (MS). Differences in the number and cargo of plasma-derived EVs have been described in MS. In this work, we have characterised the EV RNA cargo of MS patients, with particular attention to circular RNAs (circRNAs), which have attracted increasing attention for their roles in physiology and disease and their biomarker potential. (2) Methods: Plasma-derived EVs were isolated by differential centrifugation (20 patients, 8 controls), and RNA-Sequencing was used to identify differentially expressed linear and circRNAs. (3) Results: We found differences in the RNA type distribution, circRNAs being enriched in EVs vs. leucocytes. We found a number of (corrected p-value < 0.05) circRNA significantly DE between the groups. Nevertheless, highly structured circRNAs are preferentially retained in leukocytes. Differential expression analysis reports significant differences in circRNA and linear RNA expression between MS patients and controls, as well as between different MS types. (4) Conclusions: Plasma derived EV RNA cargo is not a representation of leukocytes’ cytoplasm but a message worth studying. Moreover, our results reveal the interest of circRNAs as part of this message, highlighting the importance of further understanding RNA regulation in MS.

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Piet Mondrian’s trees and the evolution in understanding multiple sclerosis, Charcot Prize Lecture 2011

Cited by 8 publications

References 54 publications

Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis

Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis

A Journey in Science: The Privilege of Exploring the Brain and the Immune System

Profiling of Plasma Extracellular Vesicle Transcriptome Reveals That circRNAs Are Prevalent and Differ between Multiple Sclerosis Patients and Healthy Controls

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