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ABSTRACT
Introduction: Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases with both licensed and off-label indications. The mechanism of action is complex and not fully understood, involving the neutralization of pathological antibodies, Fc receptor blockade, complement inhibition, immunoregulation of dendritic cells, B cells and T cells and the modulation of apoptosis.
Areas covered: First, this review describes the pharmacological properties of IVIg, including the composition, mechanism of action, and adverse events. The second part gives an overview of some of the immune-mediated polyneuropathies, with special focus on the pathomechanism and clinical trials assessing the efficacy of IVIg. A literature search on PubMed was performed using the terms IVIg, IVIg preparations, side effects, mechanism of action, clinical trials, GBS, CIDP.
Expert opinion: Challenges associated with IVIg therapy and the treatment possibilities for immune-mediated polyneuropathies are discussed. The availability of IVIg is limited, the expenses are high, and, in several diseases, a chronic therapy is necessary to maintain the immunomodulatory effect. The better understanding of the mechanism of action of IVIg could open the possibility of the development of disease-specific, targeted immune therapies.
Article highlights
IVIg is a blood product obtained from plasma pooled from thousands of healthy donors. IVIg is used in lower doses as a replacement therapy for immunodeficient patients and in doses of 1-2 g/kg for the suppression of autoimmune diseases. Besides the licensed indications, several off-label indications exist.
IVIg has a complex mechanism of action, involving the neutralization and an enhanced clearance of pathological antibodies, Fc receptor blockade, complement inhibition, a decrease in the production of inflammatory cytokines, immunoregulation of DCs, B and T cells, an enhancement of Tregs, and the modulation of apoptosis.
IVIg is generally well tolerated, with most of the side effects being mild and transient. Severe side effects, such as thrombosis, anaphylactic reaction, and kidney injury, can occur.
Immune-mediated polyneuropathies are a heterogeneous group of diseases of the peripheral nervous system. Anti-ganglioside antibodies through molecular mimicry and complement activation play a role in the pathomechanism of GBS. The pathomechanism of CIDP is not fully understood, with both cellular and humoral mechanisms involved. Several clinical trials prove the efficacy and safety of IVIg in GBS and CIDP.
Despite the considerable progress in both the supportive therapy and immunotherapy, GBS is still a life-threatening disease, resulting in a permanent disability in some 20% of the patients. The chronic forms are difficult to diagnose, and, especially in the case of a delay in the initiation of the therapy, a severe disability and an impairment of the quality of life can ensue. There is still much to do in order to improve the therapy for immune-mediated polyneuropathies.
Understanding the exact mechanism of action of IVIg in these disorders might enable the design of more specific therapies.
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Acknowledgements
We acknowledge Mr. Levente Szalárdy, MD for the linguistic correction of the manuscript.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.