title: Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study.
abstract: Common variable immunodeficiency (CVID) is the most frequent clinically expressed primary immunodeficiency in adults and is characterized by primary defective immunoglobulin production. Besides recurrent infectious manifestations, up to 20% of CVID patients develop autoimmune complications. In this study, we took advantages of the French DEFI database to investigate possible correlations between peripheral lymphocyte subpopulations and autoimmune clinical expression in CVID adult patients. In order to analyse homogeneous populations of patients with precise clinical phenotypes, we first focused on patients with autoimmune cytopenia because they represent prototypic autoantibody mediated diseases. In a secondary analysis, we have tested our conclusions including all "autoimmune" CVID patients. We describe one of the largest European studies with 311 CVID patients, including 55 patients with autoimmune cytopenia and 61 patients with clinical or serologic autoimmune expression, excluding autoimmune cytopenia. We clarify previous reports and we confirm a very significant correlation between an increased proportion of CD21(low) B cells and CVID associated autoimmune cytopenia, but independently of the presence of other autoimmune disorders or of splenomegaly. Moreover, in CVID associated autoimmune cytopenia, T cells display an activated phenotype with an increase of HLA-DR and CD95 expression and a decrease in the naïve T cell numbers. Patients with other autoimmune manifestations do not harbour this "T and B cells phenotypic picture". In view of recent findings on CD21(low) B cells in CVID and RA, we suggest that both a restricted subset of B cells and a T cell help are required for a breakdown of B cell tolerance against membrane auto antigens in CVID.
authors.affiliation: Department of Clinical Immunology and Internal Medicine, Hôpitaux Universitaires de Strasbourg et Université de Strasbourg, CNRS UPR9021, Strasbourg, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Boileau
authors.forename: Gael
authors.initials: G
authors.lastname: Mouillot
authors.forename: Laurence
authors.initials: L
authors.lastname: Gérard
authors.forename: Maryvonnick
authors.initials: M
authors.lastname: Carmagnat
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pasquali
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Korganow
mesh_terms: D000293:Adolescent; D000328:Adult; D015551:Autoimmunity / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005602:France; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult