Evaluation of B Cell and T Cell Phenotypes in CVID Patients and its Correlation with the Clinical Phenotype of the Disease: Study Protocol

Introduction: Common variable immunodeficiency is the most common symptomatic primary immune deficiency, which manifests a wide range of clinical phenotypes from recurrent infections of respiratory system to autoimmunity, gastrointestinal and lymphoproliferative disorders. Some abnormalities in T and B lymphocyte subpopulations can lead to development of clinical complications. A comprehensive study is needed to promote greater understanding of CVID’s clinical manifestations by evaluating lymphocyte abnormalities simultaneously.Aim of study: The main objective of this case-control study is to investigate the frequency and absolute count of different BCD19+, TCD4+ and TCD8+ subgroups in CVID patients as well as the proliferation response of TCD4+ cells in order to determine the possible correlation between lymphocyte abnormalities and clinical phenotypes of disease such as infection only (IO), autoimmunity (AI), chronic enteropathy (CE) and lymphoproliferation (LP). We also aim to determine the risk of developing CVID and clinical manifestations based on lymphocyte phenotype.Methods and analysis: A population of WES negative patients with CVID subdivided to 4 clinical phenotypes i.e. IO, AI, CE and LP and age and sex matched healthy controls will be examined for the frequency of subgroups of BCD19+, TCD4+ and TCD8+ lymphocytes by flow cytometry. The proliferation response of CD4+ T cells is then evaluated by CFSE test, using stimulation of isolated peripheral blood mononuclear cells with anti-CD3, anti-CD28 antibodies. Data analysis will be assessed by a parametric or nonparametric test based on normality using IBM SPSS Statistics and STATA software.Ethics and dissemination: Ethical approval of this study is received from Ethics Committee of Tehran University of Medical Sciences (ID number: IR.TUMS.VCR.REC.1396.3380) and all participants will sign the informed consent statement. Due to the wide range of variables and objectives, the findings of this study are intended to release as multiple publications in peer-reviewed journals and presented at international conferences.