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.