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.
Highlights
Common variable immunodeficiency (CVID) is a heterogeneous collection of diseases defined as hypogammaglobulinemia of unknown cause with markedly decreased IgG and IgA levels, with or without low IgM levels, displaying a lack of antibody response to vaccination
We previously reported the stability of the B-cell profile in CVID patients over time[18], we confirmed that CD21low B cells are stable in the present cohort (Fig. 4A)
This group of CVID patients suffered from thrombocytopenia, bronchiectasis and pulmonary fibrosis
Summary
Common variable immunodeficiency (CVID) is a heterogeneous collection of diseases defined as hypogammaglobulinemia of unknown cause (secondary hypogammaglobulinemia excluded) with markedly decreased IgG and IgA levels, with or without low IgM levels, displaying a lack of antibody response to vaccination It is clinically accompanied by infections, autoimmunity, granulomatous disease and, in some cases, lymphoproliferation. CD21low B-cells have been described as tissue-homing, innate-like memory cells[13] with extensive proliferation history[13,14], capable of autoreactivity[15] and with limited responsiveness[16] These puzzling CD21low B-cells have been found in increased amounts in CVID patients with autoimmune cytopenias and in patients with systemic lupus erythematosus[17], rheumatoid arthritis[15] and Sjögren’s syndrome[16]. We aimed to define the clinical, cellular and cytokine profile of the most strikingly different subgroup of CVID
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
