Reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells and diminished FOXP3 expression in patients with Common Variable Immunodeficiency: A link to autoimmunity?

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. in this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. in conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID. (C) 2009 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The Brazilian Ministry of Science and Technology (MCT)Instituto do Milenio ProgrammeUniv São Paulo, Dept Immunol, Inst Biomed Sci, Lab Imunol Clin, BR-05508900 São Paulo, BrazilUniv São Paulo, Div Clin Immunol & Allergy, Sch Med, BR-05508900 São Paulo, BrazilUniv São Paulo, LIM 60, Sch Med, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilFAPESP: 04/15887-1FAPESP: 07/07139-3Web of Scienc