title: A novel immunodeficiency characterized by the exclusive presence of transitional B cells unresponsive to CpG.
abstract: The objective of this study was to describe a novel form of primary immune disorder characterized by circulating B cells with the exclusive transitional phenotype which fail to respond to CpG stimulation. The 12-year-old male patient suffered from recurrent bacterial infections since infancy. The immunological studies were based on extensive B cell immunophenotyping, humoral in vivo response to different vaccine antigens, and in vitro proliferation and immunoglobulin production after CpG stimulation. Sequence analysis for potentially candidate genes such as IRF8, MyD88, TLR9, T-bet were performed. The patient's serum immunoglobulin levels and the specific antibody response to tetanus toxoid were normal, whereas that to polysaccharide antigens was severely impaired. Flow cytometric analysis showed that almost all patient's peripheral B cells had the transitional phenotype (CD24(bright) CD38(bright) CD27(neg)). Furthermore, the patient's B cells did not proliferate and failed to secrete immunoglobulins after in vitro CpG stimulation. Sequence analysis for TLR9, MyD88, IRF8 and T-bet showed no mutations. To our knowledge, this is the first case of a novel primary immunodeficiency mimicking the clinical phenotype of common variable immunodeficiency, with a peculiar immunological phenotype characterized by normal immunoglobulin serum levels, circulating B cells with the exclusive transitional phenotype unable to respond to CpG stimulation. This defines a novel form of primary immunodeficiency mimicking common variable immunodeficiency in the presence of normal immunoglobulin serum levels.
authors.affiliation: Clinica Pediatrica and Istituto di Medicina Molecolare A. Nocivelli, Università di Brescia, Italy. plebani@med.unibs.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Antonella
authors.initials: A
authors.lastname: Meini
authors.forename: Federica
authors.initials: F
authors.lastname: Zunino
authors.forename: Claretta Gioia
authors.initials: CG
authors.lastname: Losi
authors.forename: Roberta
authors.initials: R
authors.lastname: Gatta
authors.forename: Gemma
authors.initials: G
authors.lastname: Cattaneo
authors.forename: Luigi
authors.initials: L
authors.lastname: Nespoli
authors.forename: Maddalena
authors.initials: M
authors.lastname: Marinoni
authors.forename: Federica
authors.initials: F
authors.lastname: Capolunghi
authors.forename: Marina
authors.initials: M
authors.lastname: Vivarelli
authors.forename: Isabella
authors.initials: I
authors.lastname: Quinti
authors.forename: Rita
authors.initials: R
authors.lastname: Carsetti
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002648:Child; D017074:Common Variable Immunodeficiency / Q000175:diagnosis; D018899:CpG Islands / Q000276:immunology*; D003937:Diagnosis, Differential; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009894:Opportunistic Infections / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology; D012008:Recurrence