Decreased NETosis-related regulators in neuromyelitis optica spectrum disorders after plasma exchange

To investigate the impact of plasma exchange (PLEX) on NETosis-related regulators and their correlation with neurological improvement in NMOSD patients.

Twelve aquaporin-4 antibodies seropositive NMOSD patients were enrolled. NETosis-related regulators (myeloperoxidase [MPO], citrullinated histone H3 [CIT-H3], peptidyl arginine deiminase 4 [PAD4], neutrophil elastase [NE], CD64), pro-inflammatory cytokines (IL-1, IL-6, IL-12, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-β1) were quantitatively assessed before and after PLEX treatment. Clinical assessments included expanded disability status scale (EDSS) and visual outcome scale (VOS) scores.

Following PLEX, all patients showed symptom improvement, with 66.7 % achieving marked-to-moderate improvement (MMI) at 3 months. Key regulators, such as MPO, CIT-H3, PAD4, NE, and pro-inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-α, exhibited a statistically significant decrease immediately after the initial PLEX session (P < 0.05). Furthermore, CD64 levels demonstrated a substantial decline after the second PLEX session (P < 0.05). Conversely, the levels of anti-inflammatory cytokines, including IL-10 and TGF-β1, displayed an ascending trend post-PLEX. In clinical relevance analysis, among patients who reached MMI, the reductions in MPO, IL-1, and IL-6 exhibited statistically significant differences when compared to patients in the mild-to-no improvement group (P < 0.05). Pearson correlation analysis revealed that the percentage reduction in IL-6 levels after PLEX was positively correlated with the percentage reduction in patient EDSS/VOS scores (r = 0.638, P < 0.05).

This study highlights that reduced levels of NETosis-related regulators after PLEX contribute to clinical improvement, suggesting the potential involvement of NETosis in the acute neurological impairment observed in NMOSD.