The specific hypothesis is that affective and CFS symptoms due to RA are associated with increased immune–inflammatory biomarkers (IL-6, CRP, GM-CSF, TLR4, IL-10), increased RF and anti-CCP antibody levels, CD17, EOS compounds (KOR, MOR, and β-endorphin) but lowered FBXW7. This evidence concerns the gene TLR4 and myalgic encephalomeyelitis/chronic fatigue syndrome.