The Burden of Non-Infectious Organ-Specific Immunopathology in Pediatric Common Variable Immunodeficiency.

The pediatric common variable immunodeficiency (CVID) is the most frequent symptomatic antibody production defect characterized by infectious and non-infectious autoimmune, inflammatory, and lymphoproliferative complications. The background for CVID-related organ-specific immunopathology is associated with immune dysregulation and immunophenotypic biomarkers with expansion of CD21low B cells, and dysfunctional memory B cell, follicular T cell, and regulatory T cell compartments. The ever-increasing progress in immunogenetics shows the heterogeneity of genetic background for CVID related to the complexity of clinical phenotypes. Multiple systemic modulatory pathways are determined by variants in such genes as or gene encoding for BAFF-R, -4, , and , and or . The organ-specific immunopathology encompasses a spectrum of disorders associated with immune dysregulation, such as granulomatous interstitial lung disease, hepatocellular nodular regenerative hyperplasia, enteropathy, neuropathy, endocrinopathies, and dermatoses. This review is aimed to define and delineate the organ-specific immunopathology in pediatric CVID. It is also conducted to gather data facilitating a better understanding of complex and heterogeneous immunophenotypes in the context of immune dysregulation mechanisms and genetic background determining manifestations of the disease and implicating personalized targeted therapies with biological agents.