Immunophenotypic and functional analysis of lymphocyte subsets in common variable immunodeficiency patients without
Farzaneh Tofighi Zavareh1,2,3, Abbas Mirshafiey1,2, Reza Yazdani1,3,4
1Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Insights
Common variable immunodeficiency (CVID) involves lymphocyte abnormalities. Genetically unsolved CVID patients show distinct B and T cell changes, suggesting these alterations are not solely due to genetic mutations.
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.
Abstract:
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 CD21low and transitional B cells, effector memory (EM) and terminally differentiated effector memory (TEMRA ) CD4+ T-cell subsets as well as total, EM, TEMRA , 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.
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