Immunophenotypic and functional analysis of lymphocyte subsets in common variable immunodeficiency patients without monogenic defects

Common variable immunodeficiency (CVID) is accompanied by various lymphocyte abnormalities believed to be mostly responsible for disease features in patients with no diagnosed monogenic defects. Here, we evaluated the association of B and T lymphocyte abnormalities with the incidence of CVID. Twenty-six genetically unsolved CVID patients were examined for B and T lymphocyte subsets by flow cytometry and CD4⁺ T-cell proliferation by carboxyfluorescein succinimidyl ester (CFSE) test. We detected a reduction in total, naive, memory B cells and plasmablasts, and also total, naive, central memory and regulatory CD4⁺ T cells, besides naive CD8⁺ T cells. There was an increase in CD21^low and transitional B cells, effector memory (EM) and terminally differentiated effector memory (T_EMRA ) CD4⁺ T-cell subsets as well as total, EM, T_EMRA , activated and cytotoxic CD8⁺ T cells among non-monogenic CVID patients. CD4⁺ T-cell proliferation response was reduced regarding both division index and percent divided. In conclusion, regarding the similarity of lymphocyte abnormalities between patients without genetic defects and those with monogenic defects, genetic mutations are not responsible for these specific lymphocyte changes. However, the novel correlations observed between lymphocyte alterations among genetically unsolved CVID patients may serve as a guide to predict the potential of future CVID development for hypogammaglobulinemia children.