Polyclonal immunoglobulin G for autoimmune demyelinating nervous system disorders

Buttmann, Mathias; Kaveri, Srini V.; Hartung, Hans‐Peter

doi:10.1016/j.tips.2013.05.009

Cited by 25 publications

(23 citation statements)

References 199 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is, therefore, surprising that inflammation as target for treatment has been relatively scarcely considered, particularly, since recent years have seen a rapid development of various immune modulators for less rare diseases, such as multiple sclerosis (Bittner & Wiendl, 2016;Buttmann et al, 2013;Deiss et al, 2013). Most of these diseases are of very rare incidence, with the typical fate of orphan diseases lacking a specific therapy.…”

Section: M P L I C a T I O N Fo R T R E A T M E N T : T He Bird Imentioning

confidence: 99%

“…Many of the experimental treatment approaches developed in rodents as exemplified above presently implicate gene therapy, cell transplantation, or a combination of both. It is, therefore, surprising that inflammation as target for treatment has been relatively scarcely considered, particularly, since recent years have seen a rapid development of various immune modulators for less rare diseases, such as multiple sclerosis (Bittner & Wiendl, 2016;Buttmann et al, 2013;Deiss et al, 2013).…”

Section: M P L I C a T I O N Fo R T R E A T M E N T : T He Bird Imentioning

confidence: 99%

“…This review article focuses on the contribution of inflammation in various genetic diseases of the CNS. Based on a predominantly deleterious effect of inflammatory reactions, treatment opportunities using existing and well-established immunomodulatory therapies, initially developed for multiple sclerosis and other primarily inflammatory diseases, may emerge (Bittner & Wiendl, 2016;Buttmann, Kaveri, & Hartung, 2013;Deiss, Brecht, Haarmann, & Buttmann, 2013). This may be of particular clinical relevance by offering yet unconsidered opportunities to mitigate the usually heavy burden related to genetically mediated CNS disorders.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Neuroinflammation as modifier of genetically caused neurological disorders of the central nervous system: Understanding pathogenesis and chances for treatment

Groh

Martini

2017

Glia

View full text Add to dashboard Cite

Genetically caused neurological disorders of the central nervous system (CNS) are usually orphan diseases with poor or even fatal clinical outcome and few or no treatments that will improve longevity or at least quality of life. Neuroinflammation is common to many of these disorders, despite the fact that a plethora of distinct mutations and molecular changes underlie the disorders. In this article, data from corresponding animal models are analyzed to define the roles of innate and adaptive inflammation as modifiers and amplifiers of disease. We describe both common and distinct patterns of neuroinflammation in genetically mediated CNS disorders and discuss the contrasting mechanisms that lead to adverse versus neuroprotective effects. Moreover, we identify the juxtaparanode as a neuroanatomical compartment commonly associated with inflammatory cells and ongoing axonopathic changes, in models of diverse diseases. The identification of key immunological effector pathways that amplify neuropathic features should lead to realistic possibilities for translatable therapeutic interventions using existing immunomodulators. Moreover, evidence emerges that neuroinflammation is not only able to modify primary neural damage-related symptoms but also may lead to unexpected clinical outcomes such as neuropsychiatric syndromes.

show abstract

Section: M P L I C a T I O N Fo R T R E A T M E N T : T He Bird Imentioning

confidence: 99%

Section: M P L I C a T I O N Fo R T R E A T M E N T : T He Bird Imentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Neuroinflammation as modifier of genetically caused neurological disorders of the central nervous system: Understanding pathogenesis and chances for treatment

Groh

Martini

2017

Glia

View full text Add to dashboard Cite

show abstract

“…In neurology, IVIG serves as a mainstay therapy in immune‐mediated neuropathies and has been shown to be equally effective as plasmapheresis in Guillain‐Barré Syndrome and myasthenic crisis . In multiple sclerosis, clinical trials applying different dose regimens and study designs (for review see), yielded inconclusive results. More recently, IVIG has gained some attention as a treatment option for special forms of inflammatory CNS conditions, which are characterized by pathognomonic autoantibody signatures such as neuromyelitis optica, yet larger controlled trials are still lacking.…”

Section: Introductionmentioning

confidence: 99%

Dose‐dependent inhibition of demyelination and microglia activation by IVIG

Winter

Baksmeier

Steckel

et al. 2016

Ann Clin Transl Neurol

View full text Add to dashboard Cite

ObjectiveIntravenous immunoglobulin (IVIG) is an established treatment for numerous autoimmune conditions. Clinical trials of IVIG for multiple sclerosis, using diverse dose regimens, yielded controversial results. The aim of this study is to dissect IVIG effector mechanisms on demyelination in an ex vivo model of the central nervous system (CNS)‐immune interface.MethodsUsing organotypic cerebellar slice cultures (OSC) from transgenic mice expressing green fluorescent protein (GFP) in oligodendrocytes/myelin, we induced extensive immune‐mediated demyelination and oligodendrocyte loss with an antibody specific for myelin oligodendrocyte glycoprotein (MOG) and complement. Protective IVIG effects were assessed by live imaging of GFP expression, confocal microscopy, immunohistochemistry, gene expression analysis and flow cytometry.Results IVIG protected OSC from demyelination in a dose‐dependent manner, which was at least partly attributed to interference with complement‐mediated oligodendroglia damage, while binding of the anti‐MOG antibody was not prevented. Staining with anti‐CD68 antibodies and flow cytometry confirmed that IVIG prevented microglia activation and oligodendrocyte death, respectively. Equimolar IVIG‐derived Fab fragments or monoclonal IgG did not protect OSC, while Fc fragments derived from a polyclonal mixture of human IgG were at least as potent as intact IVIG.InterpretationBoth intact IVIG and Fc fragments exert a dose‐dependent protective effect on antibody‐mediated CNS demyelination and microglia activation by interfering with the complement cascade and, presumably, interacting with local immune cells. Although this experimental model lacks blood–brain barrier and peripheral immune components, our findings warrant further studies on optimal dose finding and alternative modes of application to enhance local IVIG concentrations at the site of tissue damage.

show abstract

“…Based on observations in basic research, animal models, and patient studies, it was proposed that IVIg provides benefit to patients with autoimmune disorders via several mutually nonexclusive mechanisms: inhibition of activation of macrophages, dendritic cells, and pathogenic T cells such as Th1 and Th17 cells; expansion of regulatory T cells; modulation of B cell responses and inhibition of pathogenic autoantibody production; suppression of production of inflammatory cytokines and stimulation of anti-inflammatory cytokines; and neutralization of pathogenic autoantibodies via anti-idiotypes and inhibition of activation of endothelial cells and complement [2]. These data, a proven track record of minimal side effects in treated patients, and promising results obtained with experimental models of MS and several case reports prompted the initiation of clinical trials exploring the utility of IVIg therapy in RRMS ( Figure 1).…”

mentioning

confidence: 99%