Pathogenic and clinical implications of serum protein biomarkers in idiopathic transverse myelitis

Abstract

Abstract Background Idiopathic transverse myelitis (ITM) is related to central nervous system inflammatory demyelinating diseases (CIDDs). However, its pathogenesis is still largely unknown and clinically applicable monitoring biomarker is lacking. We investigated serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) in patients with ITM to unravel the pathogenetic disease characteristics and clinical implications of these markers. Methods We prospectively recruited patients with ITM and CIDDs—MS and NMOSD—with acute (≤ 2 months) transverse myelitis attacks and healthy controls (HCs) between July 2018 and April 2020. We measured sNfL and sGFAP levels using ultrasensitive single-molecular arrays, examined their associations with clinical parameters, and compared them according to lesion volume between disease groups during attacks. Results A total of 119 participants were analyzed (70 with ITM [12 with attacks; 58 in remission], 11 with anti-aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4 + NMOSD), eight with multiple sclerosis (MS), and 30 HCs). Compared to HCs (median, sNfL: 10.92 pg/mL, sGFAP: 104.94 pg/mL), ITM patients showed higher sNfL and sGFAP during acute attack (sNfL: 20.57 pg/mL, p < 0.001, sGFAP: 130.76 pg/mL, p = 0.024), while those in remission (sNfL: 14.64 pg/mL, p = 0.944, sGFAP: 99.71 pg/mL, p > 0.999) did not. Multivariable analyses showed that both serum biomarkers were associated with acute attacks in ITM patients. ITM patients showed lower sGFAP/volume (median, 273.35 pg/mL/cm3) than AQP4 + NMOSD patients (1317.56 pg/mL/cm3, p = 0.011) during acute attack. Conclusions Both sNfL and sGFAP reliably reflect disease activity in ITM. Our analyses show no ongoing inflammation during remission and less damage to astrocytes in ITM than in AQP4 + NMOSD, suggesting that a substantial proportion of ITM may not share the pathogenesis of MS or NMOSD.