Nodopathies, paranodopathies, and juxtaparanodopathies: from immunopathology to neurophysiological biomarkers in autoimmune neuropathy.

The node of Ranvier and its adjacent paranodal and juxtaparanodal regions are essential for saltatory nerve conduction and axonal integrity. Although rare, autoimmune nodopathies carry a high burden of disability when treatment is delayed and are frequently misdiagnosed as classical inflammatory neuropathies such as CIDP. The identification of domain-specific autoantibodies, targeting neurofascin-186 (NF186) and gliomedin at the node, neurofascin-155 (NF155), contactin-1 (CNTN1) and contactin-1 associated protein (Caspr1) at the paranode, and Caspr2 at the juxtaparanode, has redefined immune-mediated neuropathy classification, establishing Autoimmune Nodopathies (AN) as a new disease entity. The classification of AN in this Research Topic follows the EAN/PNS Guidelines, reflecting the growing international consensus on this emerging disease entity. Within this spectrum, nodopathies, paranodopathies, and juxtaparanodopathies may be distinguished on immunopathological grounds.Critically, each entity carries a discrete IgG subclass profile: complement-activating IgG1 and IgG3 antibodies predominate in nodopathies, while non-complement-fixing IgG4 antibodies drive paranodopathy, yielding divergent effector mechanisms, histopathological signatures, and therapeutic responses. Early and accurate recognition is essential, as delayed treatment risks irreversible axonal loss, significant morbidity, and mortality.A central diagnostic challenge remains the rapid and reliable confirmation of disease-specific autoantibodies, while the underlying immunological processes driving disease, including autoreactive B-cell responses, T-cell-dependent mechanisms, and the transition from acute to chronic immune activation, remain incompletely understood. The growing clinical recognition of AN as a misdiagnosed mimic of CIDP, alongside advances in targeted immunotherapy, makes this a critical moment to consolidate current evidence and define future research priorities.Autoimmune nodopathies share key immunological effector pathways with CNS demyelinating diseases, including B cell-driven autoimmunity and complement activation, offering comparative insights relevant to the broader neuroimmunology field and informing therapeutic strategies across immune-mediated neurological conditions. Yet, although CNS symptoms have been described in AN, they remain less characterised. In the neuroimmunology clinic, AN increasingly features as a diagnostic differential alongside NMOSD and autoimmune encephalitis, underscoring the need for a unified understanding of autoantibody-mediated neurological disease across both the central and peripheral nervous systems.This Research Topic explores the immunological foundations of serological diagnosis and disease pathogenesis across the spectrum of AN.The Topic Editors welcome original research, systematic reviews, case series, and expert perspectives on:• Immunopathology and autoantibody profiles across the spectrum of AN• IgG subclass-dependent effector mechanisms and their clinical correlates• Electrophysiological studies as a biomarker of immune-mediated conduction failure• Differentiation from classical inflammatory neuropathies such as CIDP• Emerging immunotherapy strategies including B cell depletion and complement inhibition• Comparative neuroimmunology of AN and CNS autoimmune disorders, including NMOSD and autoimmune encephalitis, with focus on shared B cell-driven mechanisms and therapeutic targetsContributions that bridge translational neuroimmunology and clinical neurophysiology to support early diagnostic and therapeutic decision-making are particularly encouraged, with the aim of building a consolidated evidence base to guide diagnostic standardisation and therapeutic decision-making in clinical practice. Topic editors: Marcus Vinícius Magno Gonçalves, Luise Appeltshauser Source: https://www.frontiersin.org/research-topics/82282/nodopathies-paranodopathies-and-juxtaparanodopathies-from-immunopathology-to-neurophysiological-biomarkers-in-autoimmune-neuropathy