ABSTRACT Background Lymphoplasmapheresis (LPE), an innovative hemopurification technique that integrates conventional plasma exchange (PE) with lymphopheresis, has demonstrated efficacy in various neuroimmune disorders by removing excessive or dysfunctional lymphocytes and pathological components from plasma. This study aimed to unveil the mechanisms of LPE and provide additional clinical evidence supporting its use in the acute treatment of steroid‐refractory NMOSD. Methods This study included 105 acute‐stage steroid‐refractory NMOSD patients. The efficacy and potential mechanisms of LPE were clarified by monitoring severity scores, clinical laboratory parameters, immune cell subsets, and cytokine levels. Results In the retrospective cohort, LPE proved effective in treating acute steroid‐refractory NMOSD and was non‐inferior to PE. In the prospective cohort, LPE significantly decreased Expanded Disability Status Scale (EDSS) and Activities of Daily Living (ADL) scores ( p < 0.05). In both cohorts, erythrocytes, hemoglobin, and platelets decreased. Notably, LPE significantly reduced the proportions of activated platelet‐adherent monocytes, plasmablasts, and memory B cells, while increasing that of naive CD8 + T cell subsets ( p < 0.001). Additionally, LPE significantly reduced the levels of aquaporin‐4 antibody (AQP4‐Ab), fibrinogen, erythrocyte sedimentation rate, C‐reactive protein, complements, immunoglobulin, and proinflammatory cytokines ( p < 0.05). Conclusion While further validation is warranted, our findings suggest that LPE could represent a potential acute‐phase treatment strategy for patients with AQP4‐Ab + NMOSD, especially in those who are refractory to corticosteroid therapy.
Zeng et al. (2025) studied this question.