Monogenic CVID characterized by impaired self-tolerance and an autoimmune phenotype include ICOS [54], LRBA [55, 56], CTLA-4 [57], NF-kappa B1, and NF-kappa B2 [17] deficiencies, associated with a strikingly high prevalence of a wide spectrum of autoimmune disorders ranging from 31 to 76% of pediatric CVID cases compared to 10.2% of CVID patients in the USIDNET Registry [58]. Here, ICOS is linked to common variable immunodeficiency.