Chronic acquired neuropathies of unknown origin are classified as chronic inflammatory demyelinating
polyneuropathies (
CIDP) and chronic idiopathic axonal
polyneuropathies (CIAP). The diagnosis can be very difficult, although it has important therapeutic implications since
CIDP can be improved by immunomodulating treatment. The aim of this study was to examine the possible abnormalities of nodal and paranodal regions in these two types of neuropathies. Longitudinal sections of superficial peroneal nerves were obtained from biopsy material from 12 patients with
CIDP and 10 patients with CIAP and studied by immunofluorescence and in some cases electron microscopy. Electron microscopy revealed multiple alterations in the nodal and paranodal regions which predominated in Schwann cells in
CIDP and in axons in CIAP. In
CIDP paranodin/Caspr immunofluorescence was more widespread than in control nerves, extending along the axon in internodes where it appeared intense. Nodal channels Nav and KCNQ2 were less altered but were also detected in the internodes. In CIAP paranodes, paranodin labeling was irregular and/or decreased. To test the consequences of acquired primary Schwann cells alteration on axonal
proteins, we used a mouse model based on induced deletion of the
transcription factor Krox-20 gene. In the demyelinated sciatic nerves of these mice we observed alterations similar to those found in
CIDP by immunofluorescence, and immunoblotting demonstrated increased levels of paranodin. Finally we examined whether the alterations in paranodin immunoreactivity could have a diagnosis value. In a sample of 16 biopsies, the study of paranodin immunofluorescence by blind evaluators led to correct diagnosis in 70 ± 4% of the cases. This study characterizes for the first time the abnormalities of nodes of Ranvier in CIAP and
CIDP, and the altered expression and distribution of nodal and paranodal
proteins. Marked differences were observed between
CIDP and CIAP and the alterations in paranodin immunofluorescence may be an interesting tool for their differential diagnosis.