Whilst our numbers are small and require further validation in additional kindreds, overactivity of Tfh-effector cells would be consistent with the spontaneous development of germinal centers in CTLA4-deficient mice (37) and might suggest that in addition to the defect in negative regulation due to reduced expression of CTLA4, Tfh effector cells might drive increased germinal centre output and possibly contribute to the increased propensity toward autoimmunity in these patients. This evidence concerns the gene CTLA4 and Autoimmunity.