Antibody‐ and macrophage‐mediated segmental demyelination in chronic inflammatory demyelinating polyneuropathy: clinical, electrophysiological, immunological and pathological correlates

Abstract

Background and purpose Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous autoimmune disorder critically lacking diagnostic biomarkers. Autoantibodies to nodal and paranodal components have recently been described in a small subset of patients. Here, the diagnostic value of immune reactivity toward the myelin compartment was investigated. Methods Ninety‐four French CIDP patients were retrospectively studied. The reactivity toward the peripheral nerve was investigated. Sural nerve biopsies were examined by electron microscopy and immunofluorescence. Results Twenty‐one patients (22%) and three patients (3%) presented with a strong immunoglobulin G or immunoglobulin M reactivity respectively against the myelin compartment. The clinical, electrophysiological and morphological features were examined in nine of these patients for whom sural nerve biopsies were available. Seven patients were electrodiagnosed with definite CIDP, one with possible CIDP and one was unclassifiable but sural nerve biopsy argued for CIDP diagnosis. Electron microscopy of sural nerve biopsies demonstrated the presence of macrophage‐mediated demyelination restricted to the internode in all nine patients. Immunolabelling for voltage‐gated sodium channels, myelin and axonal markers confirmed the presence of segmental demyelination and of remyelination. The nodal and paranodal regions, however, were unaffected in these patients. Nerve conduction studies corroborated the multifocal and segmental profile, and seven patients showed increased duration of proximal (1.5–5.1 times) and/or distal (1.2–3.4 times) compound muscle action potential in at least two nerves. Conclusion Antibody‐ and macrophage‐mediated demyelination appears responsible for conduction alterations in CIDP patients and nerve immunostaining assays may serve as a supportive diagnostic biomarker.

Autoantibody screening in Guillain-Barré Syndrome

“…This observation is in agreement with previous findings: Vallat et al detected that a significant percentage of CIDP and GBS patients (about 25%) presented with IgG or IgM reactivity against myelin and that the staining patterns on Schwann cells were diverse, suggesting that diverse myelin antigens are being recognized by autoantibodies. 26 Our study also confirms, in a well-characterized GBS cohort, that gangliosides are the most frequent specific antigens in GBS patients and that they associate to specific disease variants. The value of testing anti-ganglioside antibodies in the GBS routine clinical care is controversial, but it is clear that some antibodies are associated with specific clinical phenotypes.…”

Pathological Findings in Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Single-Center Experience

“…Finally, it should be considered that pathological heterogeneity could reflect different mechanisms of immune responses involved in CIDP. Supporting this hypothesis is the recent discovery that some immune-mediated neuropathies, usually classified as CIDP, are caused by antibodies that alter the ultrastructural organization of the paranodes without inflammation or overt demyelination [24,25].…”

“…Furthermore, normal aspects of nerve biopsy, when associated with the absence of clinical and electrophysiological sensory involvement, occur in pure motor CIDP, which has been suggested to represent a distinct nosological entity [5,34,35]. Finally, the absence of lesions in nerve biopsy can be explained with the hypothesis that in some forms of CIDP the loss of function of nerve fibers is not attributable to morphological changes, as demyelination, axonal degeneration or paranodal dismantling, but to the failure of conduction caused by antibodies blocking ion channels [24,29].…”

MBP‐activated autoimmunity plays a role in arsenic‐induced peripheral neuropathy and the potential protective effect of mecobalamin

“…Inhibition of microglial activation and neuroinflammation in spinal cord underlay the effect of ammoxetine attenuating diabetic neuropathic pain 19 . Notably, chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory neuropathy characterized by myelin loss and/or axonal damage, similar with the morphological alteration of AIPN 10,20 . A growing list of auto‐antibodies were found in CIDP patient serum, which targeted peripheral nerve components and probably exerted a pathogenic effect through autoimmune inflammation 21,22 .…”

“…19 Notably, chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory neuropathy characterized by myelin loss and/or axonal damage, similar with the morphological alteration of AIPN. 10,20 A growing list of auto-antibodies were found in CIDP patient serum, which targeted peripheral nerve components and probably exerted a pathogenic effect through autoimmune inflammation. 21,22 The possible antigenic self-targets included myelin protein 0, myelin protein 2, peripheral myelin protein 22, and myelin basic protein (MBP).…”