Analysis of Soluble Interleukin‐2 Receptor as a Prognostic Biomarker in NMOSD and MOGAD

Objective Soluble interleukin‐2 receptor (sIL‐2R) is a biomarker for T cell activity. T cells are involved in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) pathogenesis. However, sIL‐2R has so far not been evaluated in these conditions. Here, we compared sIL‐2R levels in serum and cerebrospinal fluid (CSF) of patients with aquaporin‐4‐IgG‐seropositive and seronegative (AQP4‐IgG+/−) NMOSD, MOGAD, and noninflammatory neurologic disorders (NINDs), and assessed the prognostic value of sIL‐2R for future attacks. Methods Retrospective analysis of real‐world data of patients treated at Charité—Universitätsmedizin Berlin was conducted (45 MOGAD, 14 AQP4‐IgG+NMOSD, 10 AQP4‐IgG−NMOSD, 69 NINDs) between 2010 and 2024. Mean (SD) follow‐up time was 40 (35) months. sIL‐2R differences were assessed by linear mixed models. Cox regression analysis was performed to investigate the predictive value for subsequent attacks. Results Serum sIL‐2R was higher in AQP4‐IgG+NMOSD (estimated marginal mean [EMM] 802 IU/mL) and MOGAD (569 IU/mL) compared to NINDs (404 IU/mL). In patients with a first manifestation of MOGAD, but not NMOSD, serum sIL‐2R (HR = 9.07 [95% CI 1.37–60.01]) and CSF sIL‐2R (HR = 3.27 [95% CI 0.61–17.45]) levels were predictive for subsequent attacks. Interpretation Serum sIL‐2R is elevated in AQP4‐IgG+NMOSD and MOGAD and may be a prognostic biomarker for a relapsing disease course in MOGAD.