Intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): mechanisms of action and clinical and genetic considerations

ABSTRACT

Introduction

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune peripheral nerve disorder that is characterized by subacute onset, progressive or relapsing weakness, and sensory deficits. Proven treatments include intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange. This review focuses on the mechanisms of action, pharmacodynamics, genetic variations, and disease characteristics that can affect the efficacy of IVIg.

Areas covered

The proposed mechanisms of action of IVIg that can mediate its therapeutic effects are reviewed. These include anti-idiotypic interactions, inhibition of neonatal Fc receptors (FcRn), anti-complement activity, upregulation of inhibitory FcγRIIB receptors, and downregulation of macrophage activation or co-stimulatory and adhesion molecules. Clinical and genetic factors that can affect the therapeutic response include misdiagnosis, degree of axonal damage, pharmacokinetic variability, and genetic variations.

Expert opinion

The mechanisms of action of IVIg in CIDP and their relative contribution to its efficacy are subject of ongoing investigation. Studies in other autoimmune neurological conditions, in addition, highlight the role of key immunopathological pathways and factors that are likely to be affected. Further investigation into the pathogenesis of CIDP and the mechanisms of action of IVIg may lead to the development of improved diagnostics, better utilization of IVIg, and more targeted and effective therapies.

KEYWORDS:

• Neurology
• autoimmune disease
• intravenous immunoglobulin
• chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

Article highlights

• IVIg has multiple putative immunomodulatory effects that could contribute to its efficacy in the treatment of CIDP.

• The therapeutic effects of IVIg can be mediated by anti-idiotypic interactions, inhibition of FcRn, anti-complement activity, upregulation of inhibitory FcγRIIb receptors, and downregulation of macrophage activation and co-stimulatory and adhesion molecules.

• Clinical factors such as misdiagnosis, degree of axonal damage, and variability in pharmacokinetics or bioavailability can affect responsiveness in individual patients.

• Several genetic variations have been linked to responsiveness to IVIg.

• Additional studies to clarify the mechanism of IVIg in CIDP could lead to the development of improved diagnostics, better utilization of IVIg, and more targeted therapies.

Acknowledgments

The authors acknowledge Michael K James (Grifols) for medical writing, and Jordi Bozzo (Grifols) for editorial support.

Declaration of interest

M Dalakas has received consultancy fees from Alexion, Sanofi, Grifols, Argenx, Dysimmmune Diseases Foundation, Elsevier and CSL. He serves as Deputy Editor for TAND and Associate Editor for Neurology. N Latov has received consultancy fees from Pfizer, Takeda, Grifols, Immunovant, Argenx, Ipsen, Sanofi, and Therapath. K Kuitwaard has received unrestricted research grants from Grifols, Takeda, and Baxter/Shire, consultancy fees from Takeda, and speaker’s fees from Grifols and CSL. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The material in this article was presented as a symposium at the Peripheral Nerve Society Annual Meeting, Miami, FL, USA on 16 May 2022. The symposium and generation of this review article were sponsored by Grifols.