The pharmacological effect of CD4 downmodulation can only occur when the Fc part of Tregalizumab is cross-linked with the Fc-gamma receptor 1 (FcγRI, CD64) on monocytes.33 It could be possible that the higher CD4 downmodulation in healthy subjects compared with RA patients is caused either by a decreased binding of Tregalizumab's Fab part to CD4, by diminished expression or by modification of the FcγRI CD64. The gene discussed is CD4; the disease is rheumatoid arthritis.