title: Defective B cell response to TLR9 ligand (CpG-ODN), Streptococcus pneumoniae and Haemophilus influenzae extracts in common variable immunodeficiency patients.
abstract: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinaemia and antibody deficiency to both T dependent and independent antigens. Patients suffer from recurrent sinopulmonary infections mostly caused by Streptococcus pneumoniae and Haemophilus influenzae, but also gastrointestinal or autoimmune symptoms. Their response to vaccination is poor or absent. In this study we investigated B cell activation induced by the TLR9 specific ligand (CpG-ODN) and bacterial extracts from S. pneumoniae and H. influenzae known to stimulate several TLR. We found that B cells from CVID patients express lower levels of CD86 after stimulation with CpG-ODN, S. pneumoniae and H. influenzae extracts in combination with anti-IgM antibody and also display a lower proliferative index when stimulated with bacterial extracts. Our results point to a broad TLR signalling defect in B lymphocytes from CVID patients that may be related to the hypogammaglobulinaemia and poor response to vaccination characteristic of these patients.
authors.affiliation: Servei d'Immunologia, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Hospital Son Dureta, Palma de Mallorca, Spain.
authors.forename: Danilo
authors.initials: D
authors.lastname: Escobar
authors.forename: Jaime
authors.initials: J
authors.lastname: Pons
authors.forename: Antonio
authors.initials: A
authors.lastname: Clemente
authors.forename: Julio
authors.initials: J
authors.lastname: Iglesias
authors.forename: Verónica
authors.initials: V
authors.lastname: Regueiro
authors.forename: José A
authors.initials: JA
authors.lastname: Bengoechea
authors.forename: Nuria
authors.initials: N
authors.lastname: Matamoros
authors.forename: Joana M
authors.initials: JM
authors.lastname: Ferrer
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051940:B7-2 Antigen / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology*; D049109:Cell Proliferation; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D051940:B7-2 Antigen; C408982:CPG-oligonucleotide; D002457:Cell Extracts; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9