Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects

Dalakas, Marinos C.

doi:10.1007/s00415-006-5004-0

Cited by 15 publications

(11 citation statements)

References 56 publications

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“…Similarly, knowledge regarding association with disease subtypes is also important since our studies have implications for therapy of NPSLE, including targeting of IFN-α and consideration of IVIG administration. IVIG has successfully been used to treat anecdotal cases of NPSLE (42) as well as other neuroinflammatory and neurodegenerative disorders (43, 44). …”

Section: Discussionmentioning

confidence: 99%

Potent Induction of IFN-α and Chemokines by Autoantibodies in the Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus

Santer

Yoshio

Minota

et al. 2009

The Journal of Immunology

135

113

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Neuropsychiatric disease in systemic lupus erythematosus (NPSLE) is a poorly understood, but potentially fatal, disease manifestation. A pathogenetic role for autoantibodies is suspected, but the mechanism is unclear. Since immune complexes in SLE can stimulate IFN-α and there is strong evidence in humans and in mice that IFN-α can cause neuropsychiatric manifestations, we asked whether NPSLE patient serum and/or cerebrospinal fluid (CSF) contain abnormally high IFN-α-inducing activity. In a bioassay containing plasmacytoid dendritic cells and a source of Ag, NPSLE CSF induced significantly higher IFN-α compared with CSF from patients with multiple sclerosis or other autoimmune disease controls. When normalized for IgG concentration, NPSLE CSF was 800-fold more potent at inducing IFN-α compared with paired serum due to inhibitors present in serum. Analysis of Ig-deficient patient serum, depletion of IgG from normal serum, as well as addition of purified IgG to NPSLE CSF and serum in the bioassays revealed that one inhibitor was contained within the IgG fraction itself. In addition to IFN-α, immune complexes formed by CSF autoantibodies produced significantly increased levels of IFN-γ-inducible protein 10 (IP-10/CXCL), IL-8, and MCP-1, all of which have been reported to be elevated in CSF from NPSLE patients. Taken together, these findings are consistent with a two-step model of NPSLE whereby CSF autoantibodies bind to Ags released by neurocytotoxic Abs or other brain cell injury, and the resulting immune complexes stimulate IFN-α and proinflammatory cytokines and chemokines.

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Section: Discussionmentioning

confidence: 99%

Potent Induction of IFN-α and Chemokines by Autoantibodies in the Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus

Santer

Yoshio

Minota

et al. 2009

The Journal of Immunology

135

113

View full text Add to dashboard Cite

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“…Of note, remarkably lower levels of interferogenic activity have been observed in sera compared to CSFs of NPSLE patients. This was partially attributed to an inhibitory effect of serum IgG, providing a potential explanation for the success of intravenous immunoglobulin (IVIG) treatment in some cases of NPSLE [102] and other neurological diseases [103, 104]. In a recent study, involving 59 NPSLE patients, it was observed an association between acute flares of NP manifestations and elevated IFN α activity in the CSF [105].…”

Section: Type I Ifn and Neuropsychiatric Systemic Lupus Erythematomentioning

confidence: 99%

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

Karageorgas

Tseronis

Mavragani

2011

BioMed Research International

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Growing evidence over the last few years suggests a central role of type I IFN pathway in the pathogenesis of systemic autoimmune disorders. Data from clinical and genetic studies in patients with systemic lupus erythematosus (SLE) and lupus-prone mouse models, indicates that the type I interferon system may play a pivotal role in the pathogenesis of several lupus and associated clinical features, such as nephritis, neuropsychiatric and cutaneous lupus, premature atherosclerosis as well as lupus-specific autoantibodies particularly against ribonucleoproteins. In the current paper, our aim is to summarize the latest findings supporting the association of type I IFN pathway with specific clinical manifestations in the setting of SLE providing insights on the potential use of type I IFN as a therapeutic target.

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“…Walberer et al Alzheimer's disease, Parkinson's disease, postpolio syndrome, inclusion body myositis and amyloidosis [6] .…”

mentioning

confidence: 99%

Intravenous Immunoglobulin Reduces Infarct Volume but Not Edema Formation in Acute Stroke

Walberer

Nedelmann

Ritschel

et al. 2009

Neuroimmunomodulation

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Objectives: Intravenous immunoglobulin (IVIG) is used for treatment of immunodeficiencies and autoimmune disorders. Recently, IVIG has also been shown to reduce infarct size in acute stroke. Since edema treatment can provide secondary neuroprotective effects, we conducted the present study to evaluate whether edema reduction is the underlying cause of the neuroprotective properties of IVIG in experimental stroke. Methods: Male Wistar rats received either IVIG or placebo and were subjected to temporary middle cerebral artery occlusion. 24 h after temporary middle cerebral artery occlusion, clinical evaluation and 7.0T magnetic resonance imaging were performed. Ischemic lesion volume was determined on high-resolution T₂ images. T₂ relaxation time and midline shift assessed on magnetic resonance imaging as well as brain water content detected by the wet/dry method after 24 h were measured to quantify edema formation. Results: Pretreatment with IVIG leads to a statistically significant reduction of the ischemic lesion volume by 42% after 24 h, as compared to placebo treatment (p < 0.05). All three methods for quantifying edema formation indicated no differences between IVIG-treated and untreated animals (p > 0.05). Conclusion: These results suggest that the neuroprotective effect of IVIG is not an indirect result of edema reduction, but is caused by direct neuronal protection. Application of IVIG is a promising treatment concept for acute stroke. To further investigate this neuroprotective effect, studies on the efficacy, the safety profile and on the underlying mechanisms are required.

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Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects

Cited by 15 publications

References 56 publications

Potent Induction of IFN-α and Chemokines by Autoantibodies in the Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus

Potent Induction of IFN-α and Chemokines by Autoantibodies in the Cerebrospinal Fluid of Patients with Neuropsychiatric Lupus

Activation of Type I Interferon Pathway in Systemic Lupus Erythematosus: Association with Distinct Clinical Phenotypes

Intravenous Immunoglobulin Reduces Infarct Volume but Not Edema Formation in Acute Stroke

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