title: Phenotypic and Functional Comparison of Class Switch Recombination Deficiencies with a Subgroup of Common Variable Immunodeficiencies.
abstract: Primary antibody deficiencies (PADs) are the most common immunodeficiency in humans, characterized by low levels of immunoglobulins and inadequate antibody responses upon immunization. These PADs may result from an early block in B cell development with a complete absence of peripheral B cells and lack of immunoglobulins. In the presence of circulating B cells, some PADs are genetically caused by a class switch recombination (CSR) defect, but in the most common PAD, common variable immunodeficiency (CVID), very few gene defects have as yet been characterized despite various phenotypic classifications. Using a functional read-out, we previously identified a functional subgroup of CVID patients with plasmablasts (PBs) producing IgM only. We have now further characterized such CVID patients by a direct functional comparison with patients having genetically well-characterized CSR defects in CD40L, activation-induced cytidine deaminase (AID) and uracil N-glycosylase activity (UNG). The CSR-like CVID patients showed a failure in B cell activation patterns similar to the classical AID/UNG defects in three out of five CVID patients and distinct more individual defects in the two other CVID cases when tested for cellular activation and PB differentiation. Thus, functional categorization of B cell activation and differentiation pathways extends the expected variation in CVID to CSR-like defects of as yet unknown genetic etiology.
authors.affiliation: Department of Pediatric Hematology, Immunology and Infectious Diseases, Academic Medical Center (AMC), Amsterdam, The Netherlands. d.j.aandekerk@amc.nl.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands. d.j.aandekerk@amc.nl.
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Aan de Kerk
authors.affiliation: Department of Pediatric Hematology, Immunology and Infectious Diseases, Academic Medical Center (AMC), Amsterdam, The Netherlands.|Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Machiel H
authors.initials: MH
authors.lastname: Jansen
authors.affiliation: Department of Immunology, University Hospital of Wales Heath Park Cardiff, Cardiff, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jolles
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Centre Freiburg, Freiburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Warnatz
authors.affiliation: Department of Immunology, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Suranjith L
authors.initials: SL
authors.lastname: Seneviratne
authors.affiliation: Department of Internal Medicine, AMC, Amsterdam, The Netherlands.
authors.forename: Ineke J M
authors.initials: IJ
authors.lastname: Ten Berge
authors.affiliation: Department of Experimental Immunology, AMC, Amsterdam, The Netherlands.
authors.forename: Ester M M
authors.initials: EM
authors.lastname: van Leeuwen
authors.affiliation: Department of Pediatric Hematology, Immunology and Infectious Diseases, Academic Medical Center (AMC), Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D017074:Common Variable Immunodeficiency / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M
keywords: B cells; Primary antibody deficiencies; class switch recombination defect; common variable immunodeficiency