CD19 Deficiency Leads to Dysregulation of Phosphoinositide 3-Kinase-Protein Kinase B (PI3K/AKT) and Nuclear Factor Kappa B (NF-κB) Pathways: Implications for B-Cell Maturation and Immune Function.

Objective: CD19 is a cellular receptor belonging to the immunoglobulin (Ig) superfamily and serves as a critical signaling component in B-cells differentiation and activation. This study investigates gene expression changes in the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways in patients with CD19 deficiency. The role of CD19 in B-cell function was explored, along with its potential impact on these signaling pathways and the overall immune response. Materials and Methods: RNA samples were obtained from three patients diagnosed with CD19 deficiency, as well as heterozygous carriers and healthy controls. Gene expression profiles related to the PI3K/AKT axis and NF-κB pathway were analyzed using quantitative polymerase chain reaction (PCR). Results: The study revealed significant alterations in the expression of signaling pathway components, including PI3K, phosphoinositide-3-kinase regulatory subunit 1 (p85), TNF receptor-associated factor 2 (TRAF2), forkhead box O1 (FOXO1), and NF-κB, in CD19-deficient patients. While PI3K and NF-κB expression were significantly downregulated in these patients, CD19, p85, FOXO1, and TRAF2 expression were markedly upregulated. These changes suggest impaired B-cell function, leading to weakened immune system responses. Conclusion: CD19 deficiency disrupts B-cell receptor signaling, resulting in significant alterations in the PI3K/AKT axis and NF-κB pathways. These disruptions impair B-cell maturation and survival, ultimately leading to compromised immune responses. This study provides the first detailed molecular insights into the effects of CD19 deficiency, enhancing our understanding of how these signaling pathways regulate immune function.