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

Authors: Dalakas, MC; Latov, N; Kuitwaard, K

Affiliations: Thomas Jefferson Neuroimmunol Unit, Dept Neurol, Philadelphia, PA USA; Kapodistrian Univ Athens, Natl & Dept Pathophysiol, Athens, Greece; Weill Cornell Med Coll, Neuroimmunol Unit, New York, NY USA; Univ Med Ctr, Dept Neurol, Erasmus MC, Rotterdam, Netherlands; Albert Schweitzer Hosp, Dept Neurol, Dordrecht, Netherlands

Publication: Expert Review of Neurotherapeutics; 2023

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 Fc gamma RIIB 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.