Characteristics of serum Metrnl levels in patients with neuromyelitis optica spectrum disorder and their associations with disease activity and inflammatory biomarkers

Abstract

Background Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune inflammatory disease for which reliable biomarkers of disease activity are lacking. Meteorin-like protein (Metrnl) has not been investigated in NMOSD; this study assessed its clinical significance in NMOSD patients. Methods Serum Metrnl, interleukin (IL)-6, and IL-17A levels were quantified by enzyme-linked immunosorbent assay in 50 patients with NMOSD and 30 age- and sex-matched healthy controls (HCs) and correlated with clinical and laboratory data. Metrnl levels were also remeasured in 30 patients before and after high-dose methylprednisolone therapy, together with derived inflammatory indices. Benjamini–Hochberg false-discovery-rate (FDR) correction was applied within prespecified test families, with a sensitivity power analysis. Metrnl alone and a combined multimarker logistic regression model were evaluated by receiver operating characteristic (ROC) analysis, DeLong tests, bootstrap validation, calibration, and decision curve analysis. Results Serum Metrnl levels were higher in NMOSD patients than in HCs and were greater in those with mild disability than in those with moderate-to-severe disability (both p < 0.001); the increase in patients with gadolinium-enhancing lesions was nominal (p = 0.034, q = 0.068). After FDR correction, serum Metrnl levels correlated negatively with IL-6, IL-17A, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and Expanded Disability Status Scale (EDSS) score (all q < 0.05), but not with high-sensitivity C-reactive protein (hs-CRP). Metrnl alone distinguished NMOSD patients from HCs (area under the curve [AUC] 0.752), whereas a combined model of Metrnl, IL-6, IL-17A, and hs-CRP performed markedly better (AUC 0.933; DeLong p < 0.001), increasing specificity from 53.3% to 80.0% at 100% sensitivity. After methylprednisolone therapy, Metrnl, IL-6, and IL-17A levels decreased (p < 0.001) along with clinical improvement, whereas NLR, platelet-to-lymphocyte ratio, and SII remained unchanged; the decrease in Metrnl levels (median −25.5%) was the largest and was uncorrelated with changes in other biomarkers. Conclusions Serum Metrnl levels were elevated in patients with NMOSD, inversely related to disease severity and inflammatory biomarkers, and decreased after immunotherapy, supporting it as a dynamic biomarker of disease activity and a component of a multimarker diagnostic panel. The cross-sectional design precludes causal inference, and exploratory subgroup findings require external validation.