Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis.

Abstract

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51±1.36 vs. 5.24±0.53ng/mL), anti-MOG IgG (5.68±1.34 vs. 0.51±0.49ng/mL), and S100β protein (2.24±0.50 vs. 0.47±0.06) than controls (all p<0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p<0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r=-0.42, p=0.005), Stroop Color-Word (r=-0.48, p=0.004), and N-Back Total scores (r=-0.59, p<0.0001) and positively with Trail Making Test B (TMB, r=0.53, p=0.001). Negative correlation was found between levels of anti-MOG and DVR (r=-0.64, p<0.0001), N-Back Total scores (r=-0.35, p=0.03), Stroop Color-Word (r=-0.51, p=0.001), and positively with TMB (r=0.50, p=0.003). S100β levels were associated with DVR (r=-0.51, p=0.002), TMB (r=0.46, p=0.008), Stroop Color-Word (r=-0.67, p<0.0001), and N-Back Total (r=-0.52, p=0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.