AIRE and immunodeficiency disease: Monogenic HAIDs have been crucial to identifying key contributors to tolerance, e.g. the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED, alias autoimmune polyglandular syndrome type 1, APS1) due to autoimmune regulator (AIRE) mutations [9, 10], the immunodysregulation polyendocrinopathy and enteropathy X-linked (IPEX) syndrome) resulting from FOXP3 mutations [11] and ‘leaky’ (subtotal) immunodeficiency syndromes due to primary T-cell or stromal cell developmental defects [12, 13].