Expansion of Myeloid-Derived Suppressor Cells and Lymphocyte Apoptosis Beyond B-Cell Deficiency in X-Linked Agammaglobulinemia.

Abstract

X-linked agammaglobulinemia (XLA) is caused by Bruton tyrosine kinase gene mutations, leading to B-cell deficiency. This study aimed to investigate myeloid-derived suppressor cells (MDSCs) frequency, lymphocyte apoptosis and clinical significance in patients with XLA. The study comprised 46 paediatric (mean age: 9.9 ± 4.8 years) and 21 adult patients (24.6 ± 5.9 years). Total MDSCs (HLA-DR^-CD33⁺CD11b⁺) were subdivided into CD15⁺ polymorphonuclear (PMN-MDSCs) and CD14⁺ monocytic (M-MDSCs) and analysed by flow cytometry. The paediatric XLA patients had increased M-MDSCs and early apoptotic lymphocyte frequency compared to healthy subjects. The mean diagnostic delay was positively correlated with early apoptotic CD3⁺ and CD4⁺ T-cells. Seventeen patients (14 adults and 3 children) had bronchiectasis. PMN-MDSCs were higher in adult patients than in paediatric patients. Increased PMN-MDSCs in adults with XLA suggest the presence of chronic inflammation in patients with bronchiectasis. The study findings broaden understanding of XLA's complex immunopathology and highlight the need for more comprehensive immune monitoring of these patients beyond antibody production.