title: The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.
abstract: The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three groups of patients showed decreased memory B- and naïve T-cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T-cell frequency and expression of inducible T-cell co-stimulator and chemokine receptors were only significantly altered in patients with common variable immunodeficiency. Asymptomatic first-degree family members of patients demonstrated similar, albeit intermediate, alterations in naïve and memory B- and T-cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B-cell composition. Furthermore, asymptomatic relatives showed decreased levels of CD4+recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives than in healthy controls. We conclude that, in our cohort, the immunophenotypic landscape of primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients were found to have an intermediate phenotype for peripheral B- and T-cell subsets.
authors.affiliation: Clinical Immunology Research Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.|Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Belgium.|Center for Medical Genetics, Ghent University and Ghent University Hospital, Belgium.|Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.
authors.forename: Delfien J A
authors.initials: DJ
authors.lastname: Bogaert
authors.affiliation: Clinical Immunology Research Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.|Center for Medical Genetics, Ghent University and Ghent University Hospital, Belgium.
authors.forename: Marieke
authors.initials: M
authors.lastname: De Bruyne
authors.affiliation: Clinical Immunology Research Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.|Tumor Immunology Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Debacker
authors.affiliation: Center for Medical Genetics, Ghent University and Ghent University Hospital, Belgium.|Cancer Research Institute, Ghent University, Belgium.
authors.forename: Pauline
authors.initials: P
authors.lastname: Depuydt
authors.affiliation: Center for Medical Genetics, Ghent University and Ghent University Hospital, Belgium.|Cancer Research Institute, Ghent University, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Belgium.
authors.forename: Carolien
authors.initials: C
authors.lastname: Bonroy
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Belgium.|Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.affiliation: Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University Hospital, Belgium.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bordon
authors.affiliation: Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.|Department of Internal Medicine, Ghent University, Belgium.|Department of Pulmonology, Ghent University Hospital, Belgium.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.affiliation: Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Belgium.|Department of Internal Medicine, Ghent University, Belgium.|Department of Hematology, Ghent University Hospital, Belgium.
authors.forename: Tessa
authors.initials: T
authors.lastname: Kerre
authors.affiliation: Department of Medicine, The Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA and.|B Cell Biology Laboratory, Hospital del Mar Medical Research Institute, Barcelona, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
authors.affiliation: Tumor Immunology Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.|Department of Internal Medicine, Ghent University, Belgium.|Department of Pulmonology, Ghent University Hospital, Belgium.
authors.forename: Karim Y
authors.initials: KY
authors.lastname: Vermaelen
authors.affiliation: Clinical Immunology Research Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium.|Department of Pediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Belgium.
authors.forename: Filomeen
authors.initials: F
authors.lastname: Haerynck
authors.affiliation: Clinical Immunology Research Laboratory, Department of Pulmonary Medicine, Ghent University Hospital, Belgium melissa.dullaers@ugent.be.|Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium.|Department of Internal Medicine, Ghent University, Belgium.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
mesh_terms: D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D017074:Common Variable Immunodeficiency / Q000097:blood / Q000175:diagnosis*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005190:Family; D005260:Female; D006801:Humans; D017099:IgG Deficiency / Q000097:blood / Q000175:diagnosis*; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping / Q000379:methods; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007136:Immunoglobulins