Whereas this paradox may be partially explained by the interaction of TNF with other pro-inflammatory cytokines in each specific disease setting, such as IL-6 in RA versus IL-17A in SpA (Schett et al., 2013; Yeremenko et al., 2014), the present study proposes a new concept that the exact expression form of a single cytokine, in this case soluble versus tmTNF, may also contribute to determine the phenotype and pathology of a disease. The gene discussed is TNF; the disease is rheumatoid arthritis.