Lymphocytes subsets in correlation with clinical profile in CVID patients without monogenic defects

Abstract

Objectives: Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy, and lymphoproliferation. We evaluated the correlation of lymphocyte subpopulations with such manifestations.Methods: Twenty-six genetically unsolved CVID patients were subdivided into four phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE), and lymphoproliferative disorders (LP) and examined for lymphocyte subsets by flow cytometry and TCD4⁺ proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test.Results: We detected reduced memory B and increased total, effector memory (EM), cytotoxic, and activated TCD8⁺ in IO, AI and CE, decreased plasmablasts, total and naive TCD4⁺, Regulatory TCD4⁺ (Treg) and naive TCD8⁺ in IO and CE, elevated CD21^low B and terminally differentiated effector memory (T_EMRA) TCD8⁺ in IO and AI, increased helper T (Th2) and Th17 in IO, decreased Th1 in AI and defective total and naive B and central memory (CM) TCD4⁺ in CE. IO showed reduced TCD4⁺ proliferation response.Conclusions: In genetically unsolved CVID patients, increased Th2 and Th17 and reduced Treg is associated with IO, increased CD21^low B and T_EMRA TCD8⁺ and reduced Th1 is contributed to AI and reduced total and naive B, CM TCD4⁺ and naive TCD8⁺ and expanded total TCD8⁺ is correlated with CE.

Keywords: Primary immunodeficiency; clinical profile; common variable immunodeficiency (CVID); inborn errors of immunity; lymphocytes subsets; proliferation response.