Elevated serum autoantibody against high mobility group box 1 as a potent surrogate biomarker for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a complicate and progressive onset devastating neurodegenerative disease. Its pathogenic mechanisms remain unclear and there is no specific test for diagnosis. For years, researchers have been vigorously searching for biomarkers associated with ALS to assist clinical diagnosis and monitor disease progression. Some specific inflammatory processes in the central nervous system have been reported to participate in the pathogenesis of ALS. As high mobility group box 1 (HMGB1) is elevated in spinal cord tissues of patients with ALS, we hypothesized, therefore, that serum autoantibody against HMGB1 (HMGB1 autoAb) might represent an effective biomarker for ALS. Patients with ALS, Alzheimer's disease, Parkinson's disease, and healthy age-matched control subjects were recruited for this study. ALS group consisted of 61 subjects, the other groups each consisted of forty subjects. We generated a polyclonal antibody against HMGB1 and developed an ELISA-based methodology for screening serum samples of these subjects. All samples were coded for masked comparison. For statistic analyses, two-tailed Student's t-test, ANOVA, Bonferroni multiple comparison test, Spearman correlation, and receiver operating characteristic curve were applied. We discovered that the level of HMGB1 autoAb significantly increased in patients with ALS as compared with that of patients with Alzheimer's disease, Parkinson's disease, and healthy control subjects. The differences between all groups were robust even at the early stages of ALS progression. More importantly, higher HMGB1 autoAb level was found in more severe disease status with significant correlation. Our study demonstrates that serum HMGB1 autoAb may serve as a biomarker for the diagnosis of ALS and can be used to monitor disease progression.