The potential role of IgG subclass in NF155-associated nodopathy for targeting therapy: a pediatric case report highlighting the efficacy of pulsed oral corticosteroids.

BACKGROUND: The autoimmune nodopathies are a distinct subgroup of immune-mediated polyneuropathies with characteristic clinical, pathophysiological, and electrophysiological features. IgG4 is the most frequently identified subclass and is typically associated with poor responsiveness to conventional therapies such as intravenous immunoglobulin and corticosteroids. However, emerging evidence highlights the relevance of non-IgG4 subclasses (e.g., IgG1), which may confer differential treatment responsiveness and prognostic implications. CASE PRESENTATION: We report a 15-year-old boy with subacute, progressive distal sensorimotor polyneuropathy who initially fulfilled the clinical and electrophysiological criteria for the distal variant of chronic inflammatory demyelinating polyneuropathy. Despite multiple courses of IVIG, the patient's symptoms worsened, prompting further investigation for nodal/paranodal antibodies. Serum testing revealed high-titre anti-NF155 antibodies of the IgG1 subclass, the IgG4 subclass was not detected. Due to the negative results of IgG4 we have decided not to start treatment with rituximab but with high-dose pulsed oral dexamethasone which resulted in marked clinical and electrophysiological improvement over a 36-month period, with excellent tolerance and no adverse effects. CONCLUSION: Pediatric patients presenting with demyelinating polyneuropathies unresponsive to intravenous immunoglobulins should be evaluated for autoimmune nodo-paranodopathies, including subclass-specific antibody profiling. In IgG1-NF155 associated autoimmune nodopathy, pulsed oral corticosteroids may represent an effective therapeutic option, whereas the response to intravenous immunoglobulin can be suboptimal.