Toward the stratification and personalization of common variable immunodeficiency treatment

Introduction: Common Variable Immunodeficiency (CVID) represents a heterogeneous group of primary immunodeficiencies characterized by recurrent infections, hypogammaglobulinemia and increased susceptibility to autoimmune diseases and certain malignancies. The list of genetic defects underlying hypogammaglobulinemia is growing every day.Areas covered: In this paper, all identified monogenetic defects underlying CVID were summarized and their similarities and differences were discussed. To date mutation in several genes including ICOS, TNFRSF12, TNFRSF13C, TNFRSF13B, CD19, CD20, CD21, CD81, PI3K, PRKCD and LRBA have been identified to underlie CVID like phenotype. The current standard treatment for CVID is Immunoglobulin substitution. Immunomodulatory drugs for autoimmune phenotypes, HSCT for lymphoid malignancies and impaired cellular immunity are other treatments, while patient selection for these treatments are of utmost importance and justifies individualized patient treatment for CVID.Expert opinion: Genetic testing is expensive and deemed unnecessary in many patients with CVID, however if done it expands our knowledge regarding genetic defects underlying CVID. Currently, CVID is diagnosed and classified based on clinical presentation and laboratory findings. Future studies may help reclassify this heterogeneous group of diseases.