Abstract
Purpose
Common variable immunodeficiency (CVID) is the most frequent form of primary symptomatic hypogammaglobulinemia. CVID patients display a number of abnormalities in lymphocyte subpopulations including chronic T-cell activation and decreased numbers of circulating CD4+ T cells and NK cells. We and others have recently shown that CVID is associated with increased concentration of soluble CD14 (sCD14) and other factors indicating limited microbial translocation.
Methods
To address the mechanisms of chronic immune activation in CVID, we performed a detailed analysis of cytokine serum levels in 36 patients with CVID, 52 patients with selective IgA deficiency (IgAD), and 56 healthy volunteers.
Results
We show that CVID is associated with elevated serum levels of CXCL-10/IP-10, IL-1R antagonist, TNF-α, IL-10, IL-12 (p40), CCL-2/MCP-1, G-CSF, and CCL-11/eotaxin. The detected cytokine signature is consistent with an ongoing activation of cells of myeloid lineage. In contrast, the levels of cytokines typically produced by CD4+ T helper cells of Th1 (IFN-γ, IL-2), Th2 (IL-9, IL-13), and Th17 (IL-17) subtypes were suppressed in CVID patients compared to healthy donors.
Conclusions
Presented data suggest that the altered cytokine profile observed in patients with CVID may be attributed to the activation of monocyte-macrophage and granulocyte lineages, possibly driven by the translocation of bacterial components across the gastrointestinal or respiratory tracts mucosal barrier.
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Acknowledgments
Supported by grants awarded by the Czech Ministry of Health, Czech Republic (NT11414-5/2010; J.L., M.V.) and National Institutes of Health, USA (AI074438; Z.H.). UAB Center for AIDS Research (CFAR; funded by NIH grant P30 AI027767) Flow Cytometry Core was instrumental in the analysis of samples by the MILLIPLEX MAP assay. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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The authors have no conflict of interest to disclose.
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Hel, Z., Huijbregts, R.P.H., Xu, J. et al. Altered Serum Cytokine Signature in Common Variable Immunodeficiency. J Clin Immunol 34, 971–978 (2014). https://doi.org/10.1007/s10875-014-0099-z
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DOI: https://doi.org/10.1007/s10875-014-0099-z