Diagnostic insights into chronic-inflammatory demyelinating polyneuropathies

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated neuropathy with demyelination of nerve fibers as leading morphological feature. The course of disease can be chronic progressive or remitting relapsing. Whereas for acute immune-mediated neuropathies several serological markers have been identified and used successfully in clinical routine, the serological diagnosis of chronic variants such as CIDP has not yet been evolved satisfactory. The typical CIDP and its various atypical variants are characterized by a certain diversity of clinical phenotype and response to treatment. Thus, diagnostic markers could aid in the differential diagnosis of CIDP variants and stratification of patients for a better treatment response. Most patients respond well to a causal therapy including steroids, intravenous immunoglobulins and plasmapheresis. Apart from electrophysiological and morphological markers, several autoantibodies have been reported as candidate markers for CIDP, including antibodies against glycolipids or paranodal/nodal molecules. The present review provides a summary of the progress in autoantibody testing in CIDP and its possible implication on the stratification of the CIDP variants and treatment response.

Keywords: Chronic inflammatory demyelinating polyneuropathy (CIDP); antiganglioside antibody; antinodal/paranodal antibody; antisulfatide antibody.

Figure 1

Structure of the node of Ranvier and adjunct regions of a myelinated nerve fiber. Schwann cells insulate the axon of a nerve cell by tightly binding to the axolemma through septate-like junctions in the paranode (PN) region and forming the myelin sheath around the axon. The myelin loops express the neurofascin isoform 155 which interacts with the heterodimers of contactin (CNTN)-1 and contactin-associated protein (Caspr) on the axolemma, both representing major autoantigenic targets in chronic inflammatory demyelinating polyneuropathy (CIDP). Sulfatide another autoimmune target in CIDP is essential for the stabilization of the PN region. The adjacent juxtaparanodal (JPN) region is characterized by voltage-gated potassium channels on the axolemma and the presence of Caspr2 and CNTN-2 complexes. The internode (IN) region consists of the compact myelin sheath around the corresponding axon region. The non-insulated region between two adjacent Schwann cells is referred to as the node of Ranvier enriched with voltage-gated sodium channels essential for saltatory conduction.