Novel serum autoantibodies against ß-actin (ACTB) in amyotrophic lateral sclerosis

To identify novel biomarkers using the serological analysis of recombinant cDNA expression libraries (SEREX) method and to evaluate their clinical significance in amyotrophic lateral sclerosis (ALS). Serum of ALS patients were screened for autoantibodies using the SEREX method. The identified autoantibodies were validated by measuring their serum levels in 70 ALS patients, 60 normal controls (NC), and 62 Parkinson disease (PD) patients using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The clinical relevance of these autoantibodies was investigated in ALS patients. SEREX identified 16 candidate antigens including β-actin (ACTB) in addition to proteasome subunit alpha type 7 (PSMA7) that we previously reported, and serum levels of antibodies against ACTB, were significantly higher in ALS patients than in NC (p < 0.001) and PD patients (p = 0.001). Moreover, serum levels of anti-ACTB antibody were higher in advanced stage ALS patients (Stage 4 on the King's ALS clinical staging) and in those with more severe disability (ALS Functional Rating Scale revised [ALSFRS-R] score < 40.5) compared to early stage (Stage 2 [2nd region involved)]) patients and those with less severe disability (ALSFRS-R score ≥ 40.5) (p = 0.003, p = 0.014). Anti-ACTB antibody levels were also negatively correlated with ALSFRS-R score (ρ = -0.409, p = 0.001), but positively correlated with clinical disease stage (ρ = 0.355, p = 0.003), and showed a weak positive correlation with disease duration (ρ = 0.294, p = 0.014). Anti-ACTB antibodies may be a potential biomarker of ALS could indicate disease severity.