Toward the stratification and personalization of common variable immunodeficiency treatment

ABSTRACT

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.

KEYWORDS:

• Common variable immunodeficiency
• antibody deficiency
• genetic analysis

Article highlights

• CVID encompasses a heterogeneous group of PIDs characterized by recurrent infections particularly respiratory tract infections, hypogammaglobulinemia and increased susceptibility to autoimmune diseases and certain malignancies.

• CVID is the diagnosis of exclusion.

• ICOS, TNFRSF12, TNFRSF13C, TNFRSF13B, CD19, CD20, CD21, CD81, PI3K, PRKCD and LRBA have been identified to underlie CVID like phenotype.

• classification of CVID can be done into two main groups of T cell dependent defect in antibody production (ICOS mutation), T cell independent defect in B cell repertoire of antibody production (TACI, BAFF-R, CD 19, CD 21, CD 81 and CD 20 deficiency).

• T cell independent defect in antibody production can be further classified into two main groups; genetic defects resulting in decreased survival B cells (TACI, BAFF-R deficiencies) with low number of B cells and genetic defects resulting in mainly poor antibody response to antigens (CD 19, CD 21, CD 81 and CD 20 deficiencies).

• Clinical diagnosis of CVID is the approach of many centers worldwide, while novel identified genes and laboratory markers will provide helps as well as new challenges to reach the certain consensus on definition and classification of CVID.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.