Immunodeficiencies with autoimmune consequences.

Far from being mutually exclusive, immunodeficiency and autoimmunity may occur simultaneously. During the last years, analysis of Autoimmune Polyendocrinopathy--Candidiasis--Ectodermal Dystrophy (APECED) and Immunodysregulation--Polyendocrinopathy--Enteropathy--X-linked (IPEX), two rare monogenic forms of immunodeficiency associated with autoimmunity, has led to the identification of Auto Immune Regulator (AIRE) and Forkhead Box P3 (FOXP3), essential transcriptional regulators, involved in central tolerance and peripheral immune homeostasis, respectively. Characterization of the molecular and cellular mechanisms involved in APECED, and recognition that AIRE expression is sustained by effective thymopoiesis, has recently allowed to define that the autoimmunity of Omenn syndrome, a combined immunodeficiency due to defects of V(D)J recombination, also results from defective expression of AIRE. The implications of identification of the basis of autoimmunity in these rare forms of immunodeficiency have important implications for a better understanding of more common autoimmune disorders, and for development of novel therapeutic approaches.