Given the observed findings of relatively ‘normal’ cTfh levels in both genotyped and non-genotyped healthy controls, combined with the selective upregulation of IRF5 expression within cTfr of risk carriers, we surmise that risk cTfr cells are fully functional (due to elevated IRF5 expression), and are required to suppress cTfh cells in risk carriers, thus maintaining them in a presymptomatic stage of SLE. Here, IRF5 is linked to systemic lupus erythematosus.