Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia

Authors

  • J. Litzman,

    1. Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital
    2. CEITEC – Central European Institute of Technology, Masaryk University, Brno, Czech Republic
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  • J. Nechvatalova,

    1. Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital
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  • J. Xu,

    1. Department of Pathology and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
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  • O. Ticha,

    1. Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital
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  • M. Vlkova,

    1. Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital
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  • Z. Hel

    Corresponding author
    1. Department of Pathology and Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
    • Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University and St Anne's University Hospital
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Correspondence: Z. Hel, Department of Pathology, University of Alabama at Birmingham, 1825 University Boulevard, SHEL 603, Birmingham, AL 35294-2182, USA. E-mail: zhel@uab.edu

Summary

Common variable immunodeficiency (CVID), the most frequent symptomatic immunoglobulin primary immunodeficiency, is associated with chronic T cell activation and reduced frequency of CD4+ T cells. The underlying cause of immune activation in CVID is unknown. Microbial translocation indicated by elevated serum levels of lipopolysaccharide and soluble CD14 (sCD14) has been linked previously to systemic immune activation in human immunodeficiency virus/acquired immune deficiency syndrome (HIV-1/AIDS), alcoholic cirrhosis and other conditions. To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of immune cell populations and serum levels of sCD14, soluble CD25 (sCD25), lipopolysaccharide and markers of liver function in 35 patients with CVID, 53 patients with selective immunoglobulin (Ig)A deficiency (IgAD) and 63 control healthy subjects. In CVID subjects, the concentration of serum sCD14 was increased significantly and correlated with the level of sCD25, C-reactive protein and the extent of T cell activation. Importantly, no increase in serum lipopolysaccharide concentration was observed in patients with CVID or IgAD. Collectively, the data presented suggest that chronic T cell activation in CVID is associated with elevated levels of sCD14 and sCD25, but not with systemic endotoxaemia, and suggest involvement of lipopolysaccharide-independent mechanisms of induction of sCD14 production.

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