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 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/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.

Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression

“…Circulating autoantibodies may also contribute to poor cognition in RA. It has been shown that RA patients in remission had increased levels of autoantibodies targeting brain antigens, such as myelin basic protein and myelin oligodendrocyte glycoprotein, which inversely correlated with cognitive tests [88]. The same study reported increased plasma levels of central nervous system (CNS)-restricted proteins (S100β) in RA, indicating a dysfunctional blood brain barrier (BBB).…”

The interplay between immunosenescence and age-related diseases

“…During healthy aging, there is an increase in the levels of circulating autoantibodies, and this can be prematurely observed in RA. Of note, we have shown RA patients in remission had increased levels of autoantibodies specific for brain antigens, and this was inversely correlated with cognitive performance [44]. Therefore, the cognitive impairment in RA could also be explained by the detrimental action of CNS autoantibodies, as suggested by CNS demyelination observed in some RA patients [45].…”

Calcium-binding protein, S100b, in the blood as a biochemical marker of the neurological state of men in warzones

“…The participation of S100 group proteins in the formation of basic forms of congenital behavior and in the mechanisms of memory and learning has been proven experimentally (Hermann et al, 2012;Li et al, 2013;Baptista et al, 2017;Delgado-Moreno et al, 2017). Zhang et al (2009) reported a deterioration of cognitive characteristics in patients with depression and increased protein S100b, backed by Li et al (2014), who demonstrated that the S100b protein acts as a modulator of the inflamematory response of the hippocampus and plays a key role in reducing cognitive properties.…”