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), anticomplement 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.

Changes in axonal and clinical function during intravenous and subcutaneous immunoglobulin therapy in chronic inflammatory demyelinating polyneuropathy

“…The lack of significant correlation indicates that other factors than nerve excitability are involved in the clinical improvement observed from baseline to days four and 18 of the IVIg treatment cycle. Immunoglobulins affect various components of the immune system including antibody degradation, complement, and macrophage activation as well as co‐stimulatory and adhesion molecules 15 . It is possible that clinical improvement following IVIg does not depend on structural recovery of damaged nerves, but rather the removal of factors involved in CIDP pathophysiology, such as autoantibodies binding to the node of Ranvier, which can occur much faster.…”

“…Immunoglobulin is considered first line treatment in CIDP 7 administrated intravenously 8–12 or subcutaneously 13,14 . The exact mechanism of action in the treatment of CIDP has not been determined, but effects on different components of the immune system, including antibodies, the complement system, macrophage activation, co‐stimulatory and adhesion molecules has been demonstrated 15–17 . Upon treatment, a rapid improvement in clinical function has been found 18 .…”

“…13,14 The exact mechanism of action in the treatment of CIDP has not been determined, but effects on different components of the immune system, including antibodies, the complement system, macrophage activation, costimulatory and adhesion molecules has been demonstrated. [15][16][17] Upon treatment, a rapid improvement in clinical function has been found. 18 However, very sparse change was demonstrated in conventional nerve conduction studies (NCS).…”

“…Although no statistically significant changes in nerve excitability were observed, trends toward similar changes were found during IVIg treatment in the late group.No significant correlation was found between these changes in superexcitability and S2 accommodation and clinical function, although there were trends toward better performance on SSST, 10-MWT, 9-HPT and PGIC with the change in superexcitability and a better performance on SST and 10-MWT with the change in S2 accommodation.The lack of significant correlation indicates that other factors than nerve excitability are involved in the clinical improvement observed from baseline to days four and 18 of the IVIg treatment cycle. Immunoglobulins affect various components of the immune system including antibody degradation, complement, and macrophage activation as well as co-stimulatory and adhesion molecules 15. It is possible that clinical improvement following IVIg does not depend on structural recovery of damaged nerves, but rather the removal of factors involved in CIDP pathophysiology, such as autoantibodies binding to the node of Ranvier, which can occur much faster.Although other studies have shown long-term clinical improvement in CIDP patients during treatment with IVIg, only a few studies have investigated the clinical changes during a treatment cycle 5,18.…”

Parameters Associated with the Required Drug Dose of Intravenous Immunoglobulin in Stable Chronic Inflammatory Demyelinating Polyradiculoneuropathy

“…CIDP can affect children, as well as patients beyond the eighth decade of life [ 1 ]. Approximately 50% of patients have a typical disease course, which is defined as over two months progressive or relapsing-remitting, as well as symmetric motor weakness with absent or diminished reflexes accompanied with sensory deficits [ 3 ]. However, the clinical presentation of CIDP is variable, and beside typical CIDP, several variants exist [ 4 ].…”