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.

Centre of Immunology and Microbiology Regional Institute of Public Health Usti nad Labem Czech Republic

CLIP Childhood Leukemia Investigation Prague Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Cancer Immunology Institute for Cancer Research Oslo University Hospital Radiumhospitalet Oslo Norway

Department of Clinical Immunology and Allergology St Anne's University Hospital Brno Czech Republic

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

Gennet Prague Czech Republic

Institute of Clinical Immunology and Allergology University Hospital Hradec Kralove Czech Republic

Research Institute of Internal Medicine Oslo University Hospital Rikshospitalet Oslo Norway

Section of Clinical Immunology and Infectious Diseases Oslo University Hospital Rikshospitalet Oslo Norway

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Sci Rep. 2017 Feb 27;7:42569. doi: 10.1038/srep42569. PubMed

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The EuroFlow PID Orientation Tube for Flow Cytometric Diagnostic Screening of Primary Immunodeficiencies of the Lymphoid System