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Here, we evaluated the association of B and T lymphocyte abnormalities with the incidence of CVID. Twenty\u2010six genetically unsolved CVID patients were examined for B and T lymphocyte subsets by flow cytometry and CD4<jats:sup>+<\/jats:sup> T\u2010cell 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<jats:sup>+<\/jats:sup> T cells, besides naive CD8<jats:sup>+<\/jats:sup> T cells. There was an increase in CD21<jats:sup>low<\/jats:sup> and transitional B cells, effector memory (EM) and terminally differentiated effector memory (<jats:italic>T<\/jats:italic><jats:sub>EMRA<\/jats:sub>) CD4<jats:sup>+<\/jats:sup> T\u2010cell subsets as well as total, EM, <jats:italic>T<\/jats:italic><jats:sub>EMRA<\/jats:sub>, activated and cytotoxic CD8<jats:sup>+<\/jats:sup> T cells among non\u2010monogenic CVID patients. CD4<jats:sup>+<\/jats:sup> T\u2010cell 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.<\/jats:p>","DOI":"10.1111\/sji.13164","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T15:14:15Z","timestamp":1647702855000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunophenotypic and functional analysis of lymphocyte subsets in common variable immunodeficiency patients without monogenic defects"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-132X","authenticated-orcid":false,"given":"Farzaneh","family":"Tofighi Zavareh","sequence":"first","affiliation":[{"name":"Research Center for Immunodeficiencies Children\u2019s Medical Center Tehran University of Medical Sciences  Tehran Iran"},{"name":"Department of 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