Evaluation of Th17 profile in Common Variable Immunodeficiency (CVID) patients with and without autoimmunity

• Grant number: 11/22076-3
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2012
• End date: March 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Cristina Maria Kokron
• Grantee: Cristina Maria Kokron
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Common Variable Immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency, and it is characterized by increased susceptibility to infections, autoimmunity and malignancies. The pathogenesis of CVID is not well established. Among the immunologic abnormalities found in CVID patients we have defects in B cell differentiation, T cell defects, altered receptor expression and cytokine production, regulatory cell disturbances and disorders of innate immunity. Objective: To evaluate the TH17 profile of CVID patients followed at the Primary Immunodeficiency Outpatient Clinic of Clinical Immunology Division of HC-FMUSP, in order to observe if CVID patients with autoimmunity have a polarized cellular response to the TH17 profile. Patients and Methods: The study group will consist of 40 CVID patients recruited from the Clinical Immunology and Allergy Division of HC-FMUSP, being 20 with and 20 without autoimmunity. T lymphocytes characterization will be done by flow cytometry using the following panels: a panel for activation (CD3, CD4, CD8, HLA-DR, CD38, CD69, Live/dead), a panel for regulatory T cells (CD3, CD4, CD25, CD127, Live/dead, FoxP3) and a functional panel (CD3, CD4, Live/dead, TNF-±, IFN-³, IL-2, IL-17, IL-21) after 16 hours stimulation. TH1/TH2/TH17 cytokine pattern in cell culture supernatants will be performed by CBA (BD) method. IL-23 detection in patients' serum will be done by ELISA. Quantification of IL-6 and TGF-² expression by RT-qPCR will be made to evaluate a possible bias towards TH17 profile. Expected results: It is known that CVID patients with autoimmunity have an abnormal cytokine production with deviation to TH1 besides reduction of regulatory T cells. However, there is only one published paper on the TH17 cellular response in patients with hypogammaglobulinemia (which includes CVID). Knowing that TH17 cellular response is a possible inducer of autoimmunity, we expect to confirm a TH17 pattern in CVID patients with autoimmunity. (AU)