Evaluation of Peripheral Immune Activation in Amyotrophic Lateral Sclerosis

Abstract

Background: Accumulating evidence has revealed that immunity plays an important role in amyotrophic lateral sclerosis (ALS) progression. However, the results regarding the serum levels of immunoglobulin and complement are inconsistent in patients with ALS. Although immune dysfunctions have also been reported in patients with other neurodegenerative diseases, few studies have explored whether immune dysfunction in ALS is similar to that in other neurodegenerative diseases.Methods: Serum levels of immunoglobulin and complement were measured in 245 patients with ALS, 65 patients with multiple system atrophy (MSA), 60 patients with Parkinson’s disease (PD), and 82 healthy controls (HCs). A meta-analysis including data from this study was performed to evaluate the differences in the levels of immunoglobulin and complement between ALS patients and HCs. The serum levels of immunoglobulin and complement were compared between patient groups and HCs or between ALS patient groups established by age at onset, site at onset, disease duration, or disease severity. The correlations between the levels of immunoglobulin and complement and the clinical characteristics of ALS were analysed using Spearman correlation analysis.Results: The pooled results showed that patients with ALS had higher C4 levels than did HCs, and no significant differences between these two groups in IgG, IgA, IgM, or C3 levels were found. Multiple comparisons revealed that there were no significant differences between patients with ALS and other neurodegenerative diseases in IgG, IgA, IgM, C3, or C4 levels. In addition, the IgG levels were lower in early-onset ALS patients than in late-onset ALS patients and HCs. The correlations between age at onset of ALS and IgG and IgA levels were significantly positive. Moreover, spinal-onset ALS patients had lower serum IgG levels than did HCs, but no difference was found between bulbar-onset ALS patients and HCs.Conclusions: Peripheral immunity abnormalities existed in patients with ALS, and lower IgG levels were associated with early-onset ALS.