IL ‐6 Blockade May Suppress the Alternative Complement Pathway in Neuromyelitis Optica Spectrum Disorders

Objectives Neuromyelitis optica spectrum disorders (NMOSDs) are complement‐mediated autoimmune diseases of the central nervous system associated with anti‐aquaporin‐4 antibodies. While interleukin (IL)‐6 signaling is implicated in NMOSD pathophysiology, its effects on the complement system remain unclear. We investigated the impact of IL‐6 blockade on complement activation in NMOSD. Methods We analyzed patients with NMOSD followed at our institution who had stored blood samples (serum and plasma) obtained during remission. Twenty‐two patients during the remission phase were included: 12 treated with satralizumab (SAT) and 10 without biologics (Non‐bio). Results Levels of serum and plasma complement factors (Ba, factor H [FH], and sC5b‐9) during the remission phase tended to be lower in the SAT group than in the Non‐bio group, with a significant difference in serum Ba and plasma sC5b‐9 and FH. Acute‐phase serum Ba levels exceeded the reference range, indicating that the alternative pathway was activated during the acute phase and decreased during the remission phase. No relapses occurred after SAT therapy. Conclusion IL‐6 is involved in complement production and activation through the induction of inflammation; therefore, IL‐6 blockade may suppress complement production in patients with NMOSD and also inhibit activation of the alternative pathway. Our findings suggest a potential association between IL‐6 inhibition and modulation of the alternative complement pathway in NMOSD, providing new insight into its therapeutic mechanism. Limitations include small sample size and limited plasma data.