title: Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia.
abstract: Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning "bins" yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27- CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes' immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ CD4+ T-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Stuchlý
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kanderová
authors.affiliation: Department of Clinical Immunology and Allergology, St. Anne's University Hospital, Brno, Czech Republic.|Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Vlková
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Heřmanová
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Slámová
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Pelák
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.
authors.forename: Eli
authors.initials: E
authors.lastname: Taraldsrud
authors.affiliation: Centre of Immunology and Microbiology, Regional Institute of Public Health, Usti nad Labem, Czech Republic.
authors.forename: Dalibor
authors.initials: D
authors.lastname: Jílek
authors.affiliation: Institute of Clinical Immunology and Allergology, University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Pavlína
authors.initials: P
authors.lastname: Králíc Ková
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Børre
authors.initials: B
authors.lastname: Fevang
authors.affiliation: Gennet, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Trková
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Hrušák
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Froňková
authors.affiliation: Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Šedivá
authors.affiliation: Department of Clinical Immunology and Allergology, St. Anne's University Hospital, Brno, Czech Republic.|Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Litzman
authors.affiliation: CLIP - Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kalina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D005355:Fibrosis; D005434:Flow Cytometry; D006801:Humans; D000068884:Immunosenescence; D008168:Lung / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D055815:Young Adult