TNF and rheumatoid arthritis: For example, upregulation of type I IFN-response genes was observed in peripheral blood in about a half of RA patients (IFN “high” patients), although no clinical differentiation between IFN “low” and “high” patients was noted.24 The IFN signature was observed equally often in seropositive and seronegative RA patients with equal plasma levels of TNFα.