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

Area of Science:

• Immunology
• Genetics

Background:

• Common variable immunodeficiency (CVID) presents with diverse lymphocyte abnormalities, often linked to disease manifestations in patients lacking identified genetic defects.
• Understanding these lymphocyte alterations is crucial for diagnosing and managing CVID, especially in genetically unsolved cases.

Purpose of the Study:

• To investigate the association between B and T lymphocyte abnormalities and the incidence of CVID in genetically unsolved patients.
• To characterize specific B and T cell subset alterations and CD4+ T-cell proliferation in non-monogenic CVID.

Main Methods:

• Flow cytometry was used to analyze B and T lymphocyte subsets in 26 genetically unsolved CVID patients.
• Carboxyfluorescein succinimidyl ester (CFSE) assay assessed CD4+ T-cell proliferation.

Main Results:

• Reduced levels of total, naive, memory B cells, plasmablasts, and naive CD4+ and CD8+ T cells were observed.
• Increased CD21low B cells, transitional B cells, effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4+ T cells, and activated/cytotoxic CD8+ T cells were noted.
• Impaired CD4+ T-cell proliferation, indicated by reduced division index and percent divided, was detected.

Conclusions:

• The observed lymphocyte abnormalities in genetically unsolved CVID patients resemble those in monogenic CVID, suggesting these changes are not solely driven by genetic mutations.
• Novel correlations between lymphocyte alterations in these patients may help predict future CVID development in children with hypogammaglobulinemia.