Immunopathogenesis

Coyle, Patricia K.

doi:10.1007/978-3-030-24436-1_3

Cited by 2 publications

(1 citation statement)

References 222 publications

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“…MS immunopathogenesis primarily relies on dysregulated Th1 and Th17 mediated autoreactive immunity triggered by environmental pathogens or other factors with antigenic sequences similar to those found in myelin, resulting in molecular mimicry and cross-reactivity with myelin. After that, the recruitment of immune cells leads to focal inflammation and CNS damage ( 114 , 115 ). Although T cells are thought to be the primary contributors to MS immunopathogenesis, B cells play a significant role in the disease by priming T cells, enhancing brain-homing T cell autoproliferation, releasing pro-inflammatory cytokines, acting as a reservoir for Epstein-Barr virus (EBV), and producing autoantibodies against myelin antigens ( 116 ).…”

Section: Irregular Expression Of Survivin-specific Micrornas In Speci...mentioning

confidence: 99%

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

et al. 2022

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It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells’ excessively proliferative state and impaired apoptotic machinery. Survivin is an anti-apoptotic and mitotic factor that has sparked a considerable research interest in this field. Survivin overexpression has been shown to contribute significantly to the development of autoimmune diseases via autoreactive immune cell overproliferation and apoptotic dysregulation. Several microRNAs (miRNAs/miRs) have been discovered to be involved in survivin regulation, rendering the survivin-miRNA axis a perspective target for autoimmune disease therapy. In this review, we discuss the role of survivin as an immune regulator and a highly implicated protein in the pathogenesis of autoimmune diseases, the significance of survivin-targeting miRNAs in autoimmunity, and the feasibility of targeting the survivin-miRNA axis as a promising therapeutic option for autoimmune diseases.

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Section: Irregular Expression Of Survivin-specific Micrornas In Speci...mentioning

confidence: 99%

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

et al. 2022

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What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us?

Krämer

Wiendl

2022

Neurotherapeutics

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In the past two decades, monoclonal antibodies (mAbs) have revolutionized the treatment of multiple sclerosis (MS). However, a remarkable number of mAbs failed due to negative study results were withdrawn because of unexpected serious adverse events (SAEs) or due to studies being halted for other reasons. While trials with positive outcomes are usually published in prestigious journals, negative trials are merely published as abstracts or not at all. This review summarizes MS mAbs that have either failed in phase II–III trials, have been interrupted for various reasons, or withdrawn from the market since 2015. The main conclusions that can be drawn from these 'negative' experiences are as follows. mAbs that have been proven to be safe in other autoimmune conditions, will not have the same safety profile in MS due to immunopathogenetic differences in these diseases (e.g., daclizumab). Identification of SAEs in clinical trials is difficult highlighting the importance of phase IV studies. Memory B cells are central players in MS immunopathogenesis (e.g., tabalumab). The pathophysiological mechanisms of disease progression are independent of leukocyte 'outside-in' traffic which drives relapses in MS. Therefore, therapies for progressive MS must be able to sufficiently cross the blood–brain barrier. Sufficiently long trial duration and multicomponent outcome measures are important for clinical studies in progressive MS. The success of trials on remyelination-promoting therapies mainly depends on the sufficient high dose of mAb, the optimal readout for ‘proof of concept’, time of treatment initiation, and appropriate selection of patients. Failed strategies are highly important to better understand assumed immunopathophysiological mechanisms and optimizing future trial designs.

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Immunopathogenesis

Cited by 2 publications

References 222 publications

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

RETRACTED: Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for Novel Therapies

What Have Failed, Interrupted, and Withdrawn Antibody Therapies in Multiple Sclerosis Taught Us?

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