IVIg for relapsing–remitting multiple sclerosis: promises and uncertainties

Bayry, Jagadeesh; Hartung, Hans‐Peter; Kaveri, Srini V.

doi:10.1016/j.tips.2015.04.012

Cited by 16 publications

(14 citation statements)

References 12 publications

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“…Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used immunotherapeutics for the treatment of autoimmune diseases including those of neurological origin [1–4]. Various reports demonstrate that IVIG exerts beneficial effects through several mutually non-exclusive mechanisms including expansion of CD4 + Foxp3 + regulatory T cells (T reg cells) [5–10].…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy

Maddur

Stephen-Victor

Das

et al. 2017

J Neuroinflammation

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BackgroundIntravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking.MethodsTen newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4–5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA.ResultsThe fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with Treg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and Treg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. Treg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α.ConclusionTreg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. Treg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

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Section: Introductionmentioning

confidence: 99%

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy

Maddur

Stephen-Victor

Das

et al. 2017

J Neuroinflammation

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“…Despite the beneficial action in the experimental setting, the effect of treatment in humans is controversial. Some small studies were able to show protection, whereas a large multicentre, randomized, double-blind, placebo-controlled trial failed to reproduce the previous results ( 154 ).…”

Section: Fcγrs and Intravenous Immunoglobulin (Ivig)mentioning

confidence: 93%

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

2017

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Acute ischemic and traumatic injury of the central nervous system (CNS) is known to induce a cascade of inflammatory events that lead to secondary tissue damage. In particular, the sterile inflammatory response in stroke has been intensively investigated in the last decade, and numerous experimental studies demonstrated the neuroprotective potential of a targeted modulation of the immune system. Among the investigated immunomodulatory agents, intravenous immunoglobulin (IVIg) stand out due to their beneficial therapeutic potential in experimental stroke as well as several other experimental models of acute brain injuries, which are characterized by a rapidly evolving sterile inflammatory response, e.g., trauma, subarachnoid hemorrhage. IVIg are therapeutic preparations of polyclonal immunoglobulin G, extracted from the plasma of thousands of donors. In clinical practice, IVIg are the treatment of choice for diverse autoimmune diseases and various mechanisms of action have been proposed. Only recently, several experimental studies implicated a therapeutic potential of IVIg even in models of acute CNS injury, and suggested that the immune system as well as neuronal cells can directly be targeted by IVIg. This review gives further insight into the role of secondary inflammation in acute brain injury with an emphasis on stroke and investigates the therapeutic potential of IVIg.

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“…39 Other alternatives include ACTH, and in rare cases some clinicians will try IVIg. 40 • Vitamin D: The role of vitamin D both for healthy bones and more recently for regulation of the immune system in MS is becoming more concrete as further studies validate its role. Low vitamin D levels are associated with a greater risk of developing MS, 41 higher clinical relapse rates 42 and higher lesion loads on MRI.…”

Section: Adjunct Treatment Pearlsmentioning

confidence: 99%

Multiple Sclerosis

Calabresi¹,

Schiess²

2016

Semin Neurol

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It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients.

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IVIg for relapsing–remitting multiple sclerosis: promises and uncertainties

Abstract: Despite promising clinical trials, intravenous immunoglobulin (IVIg) therapy in relapsing-remitting multiple sclerosis (MS) has met with uncertainties that might be attributed to small patient cohorts, heterogeneity in the patients, dose of IVIg, or the duration and window of treatment.

Cited by 16 publications

References 12 publications

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy

Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy

Therapeutic Potential of Intravenous Immunoglobulin in Acute Brain Injury

Multiple Sclerosis

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