The landscape of common variable immunodeficiency conditions (CVID) is quickly changing as next-generation sequencing enables the discovery of new monogenic causes with CVID clinical phenotypes. The biology and the effects on the development of a dysregulated, rather than an insulated, infectious CVID phenotype are examined here for cytotoxic T lymphocyte-associated protein four (CTLA-4) differently expressed in the homology of the FDCP6 (DEF6), and lipopolysaccharide responsive beige anchor protein (LRBA).

There is a description of the broad clinical phenotype associated with these monogenic CVIDs and common treatment approaches.

The understanding and effective management of patients with CVID from those monogenic causes are essential in knowledge of their biology, clinical manifestation, and therapeutic options studied to date in patients with CTLA-4 insufficiency, DEF6 insufficiency and LRBA insufficiency.