Impaired CpG Demethylation in Common Variable Immunodeficiency Associates With B Cell Phenotype and Proliferation Rate.

摘要: Common Variable Immunodeficiency (CVID) is characterized by impaired antibody production and poor terminal differentiation of the B cell compartment, yet its pathogenesis still poorly understood. We first reported occurrence epigenetic alterations in CVID high-throughput methylation analysis CVID-discordant monozygotic twins. Data from a recent whole DNA methylome throughout different stages normal allowed us to design new experimental approach. selected CpG sites for based on two criteria: one, CpGs with potential association transcriptional status relevant genes activation differentiation; two, that undergo significant demethylation naive memory cells healthy individuals. was analyzed bisulfite pyrosequencing specific sorted subsets patients donors. observed thirds cells, govern cell-specific processes or participate signaling. The degree impairment associated extent reduction. such functionally as AICDA switched correlated lower proliferative rate. Our results reinforce hypothesis altered during contributing pathogenic mechanism function maturation CVID. In particular, deregulated control could play role defective establishment post-germinal center compartment