Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches

Abstract

Purpose of review Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity. The disorder is characterized by variable clinical and immunological manifestations, and, in a small minority of patients, a monogenic cause may be identified. In this review, we focalized on three different monogenic forms of CVID-like disease. Recent findings Activated phosphoinositide 3-kinase delta syndrome (APDS) is a rare disorder characterized by hyperactivated class I phosphatidylinositol-3 kinase (PI3K) pathway. Affected patients present with respiratory infectious episodes, impaired viral clearance and lymphoproliferation. Recently, a direct PI3K inhibitor has been approved and it showed encouraging results both in controlling clinical and immunological manifestations of the disease. On the other hand, patients with defects in CTLA-4 or LRBA gene present with life-threatening immune dysregulation, autoimmunity and lymphocytic infiltration of multiple organs. Abatacept, a soluble cytotoxic T lymphocyte antigen 4 (CTLA-4) fusion protein that acts as a costimulation modulator, has been widely implemented for affected patients with good results as bridge treatment. Summary Understanding the biological basis of CVID is important not only for enriching our knowledge of the human immune system, but also for setting the basis for potential targeted treatments in this disorder.