CTLA-4 haploinsufficiency causes a severe CVID-like monogenic IEI with predominantly immune dysregulatory features characterized by progressive B cell exhaustion and hypogammaglobulinemia, multiorgan autoimmunity (immune cytopenia, enteropathy, endocrinopathies), and chronic lymphoproliferation with lymphocytic infiltrates in several organs (brain, gut, liver, and lung) [34,35]. This evidence concerns the gene CTLA4 and common variable immunodeficiency.