Evaluation of B and T lymphocyte profile from Common Variable Immunodeficiency patients before and after immunization with protein and polysaccharide antigens

• Grant number: 09/13810-5
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2010 - March 31, 2012
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Cristina Maria Kokron
• Grantee: Cristina Maria Kokron
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Karolina Barreto Berselli Marinho ; Maíra Pedreschi

Abstract

Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinemia, impaired specific antibody production and clinically, by recurrent infections, increased susceptibility to autoimmunity and malignancies. The etiology is unknown in the vast majority of the patients. Although most patients present clinical manifestations related to antibody deficiency, several CVID patients have also impaired cellular immunity at some degree. A variety of immunologic findings have been reported in small groups of patients (abnormalities in T and B lymphocytes, dendritic cells and innate immunity). The clinical and laboratory heterogeneity observed in CVID patients reinforces the need of classification which could ease a molecular diagnosis approach. Lately there have been some classifications based on memory B cell populations. The reduction of switched memory B cell population was correlated to infections and autoimmunity. One of the hallmarks of CVID is the lack of vaccine-specific antibody production. However, several studies show that at least some of the patients are capable of producing antibodies in vitro and also in vivo. Moreover, the focus of vaccination is not only antibody production but also the generation of a strong and durable T cell response. Our group, in a former study, evaluated the lymphocyte ability to proliferate before and after tetanus immunization and we found that 86% of the patients had good cellular proliferation upon tetanus stimulation. The aim of this study is to classify CVID patients followed at Primary Immunodeficiencies Outpatient Clinic from the Clinical Immunology and Allergy Division of HC-FMUSP according to memory B cells and evaluate clinical outcome besides T and B lymphocyte profile before and after immunization with peptide and polysaccharide antigens. We will study 30 CVID patients and 15 healthy controls. Blood will be drawn before and 4 weeks after immunization with influenza and pneumococcal vaccines. Lymphocyte phenotypes will be evaluated by flow cytometry and antibody production by ELISA. B lymphocytes will be evaluated with CD19, CD21, CD38, CD27, IgD and IgM monoclonal antibodies. T lymphocytes will be evaluated with CD3, CD4, CD8, CD45RA and CCR7 monoclonal antibodies besides the presence of IFN-g, IL-2 and TNF intracellular cytokines. Besides in vitro evaluation we intend to make a clinical evaluation by comparing the number of infections before and after immunization. We expect to have a better characterization of our cohort of CVID patients in regard to baseline lymphocyte phenotyping and response to specific immunization and observe the effect these vaccines on clinical outcome. (AU)