Skip to main content
Top
Published in: Journal of Clinical Immunology 8/2014

01-11-2014 | Original Research

Altered Serum Cytokine Signature in Common Variable Immunodeficiency

Authors: Zdenek Hel, Richard P. H. Huijbregts, Jun Xu, Jana Nechvatalova, Marcela Vlkova, Jiri Litzman

Published in: Journal of Clinical Immunology | Issue 8/2014

Login to get access

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.
Literature
1.
go back to reference Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–27.PubMedCentralPubMedCrossRef Chapel H, Cunningham-Rundles C. Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions. Br J Haematol. 2009;145:709–27.PubMedCentralPubMedCrossRef
3.
go back to reference Yazdani R, Hakemi MG, Sherkat R, Homayouni V, Farahani R. Genetic defects and the role of helper T-cells in the pathogenesis of common variable immunodeficiency. Adv Biomed Res. 2014;3:2.PubMedCentralPubMedCrossRef Yazdani R, Hakemi MG, Sherkat R, Homayouni V, Farahani R. Genetic defects and the role of helper T-cells in the pathogenesis of common variable immunodeficiency. Adv Biomed Res. 2014;3:2.PubMedCentralPubMedCrossRef
4.
go back to reference Hammarström L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120:225–31.PubMedCentralPubMedCrossRef Hammarström L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol. 2000;120:225–31.PubMedCentralPubMedCrossRef
5.
go back to reference Litzman J, Nechvatalova J, Xu J, Ticha O, Vlkova M, Hel Z. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia. Clin Exp Immunol. 2012;170:321–32.PubMedCentralPubMedCrossRef Litzman J, Nechvatalova J, Xu J, Ticha O, Vlkova M, Hel Z. Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemia. Clin Exp Immunol. 2012;170:321–32.PubMedCentralPubMedCrossRef
6.
go back to reference Guazzi V, Aiuti F, Mezzaroma I, Mazzetta F, Andolfi G, Mortellaro A, et al. Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles. Clin Exp Immunol. 2002;129:346–53.PubMedCentralPubMedCrossRef Guazzi V, Aiuti F, Mezzaroma I, Mazzetta F, Andolfi G, Mortellaro A, et al. Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles. Clin Exp Immunol. 2002;129:346–53.PubMedCentralPubMedCrossRef
7.
go back to reference Vlková M, Thon V, Sárfyová M, Bláha L, Svobodník A, Lokaj J, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–9.PubMedCentralPubMedCrossRef Vlková M, Thon V, Sárfyová M, Bláha L, Svobodník A, Lokaj J, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–9.PubMedCentralPubMedCrossRef
8.
go back to reference Aspalter RM, Sewell WA, Dolman K, Farrant J, Webster AD. Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia. Clin Exp Immunol. 2000;121:506–14.PubMedCentralPubMedCrossRef Aspalter RM, Sewell WA, Dolman K, Farrant J, Webster AD. Deficiency in circulating natural killer (NK) cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia. Clin Exp Immunol. 2000;121:506–14.PubMedCentralPubMedCrossRef
9.
go back to reference Nechvatalova J, Pikulova Z, Stikarovska D, Pesak S, Vlkova M, Litzman J. B-lymphocyte subpopulations in patients with selective IgA deficiency. J Clin Immunol. 2012;32:441–8. Nechvatalova J, Pikulova Z, Stikarovska D, Pesak S, Vlkova M, Litzman J. B-lymphocyte subpopulations in patients with selective IgA deficiency. J Clin Immunol. 2012;32:441–8.
10.
go back to reference Litzman J, Vlková M, Pikulová Z, Stikarovská D, Lokaj J. T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency. Clin Exp Immunol. 2007;147:249–54.PubMedCentralPubMedCrossRef Litzman J, Vlková M, Pikulová Z, Stikarovská D, Lokaj J. T and B lymphocyte subpopulations and activation/differentiation markers in patients with selective IgA deficiency. Clin Exp Immunol. 2007;147:249–54.PubMedCentralPubMedCrossRef
11.
go back to reference Barbosa RR, Silva SP, Silva SL, Tendeiro R, Melo AC, Pedro E, et al. Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels. Clin Exp Immunol. 2012;169:263–72.PubMedCentralPubMedCrossRef Barbosa RR, Silva SP, Silva SL, Tendeiro R, Melo AC, Pedro E, et al. Monocyte activation is a feature of common variable immunodeficiency irrespective of plasma lipopolysaccharide levels. Clin Exp Immunol. 2012;169:263–72.PubMedCentralPubMedCrossRef
12.
go back to reference Sandler NG, Douek DC. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012;10:655–66.PubMedCrossRef Sandler NG, Douek DC. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012;10:655–66.PubMedCrossRef
13.
go back to reference Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010;16:703–11.PubMedCrossRef Agarwal S, Mayer L. Gastrointestinal manifestations in primary immune disorders. Inflamm Bowel Dis. 2010;16:703–11.PubMedCrossRef
14.
go back to reference Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (pan-american group for immunodeficiency) and ESID (european society for immunodeficiencies). Clin Immunol. 1999;93:190–7.PubMedCrossRef Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (pan-american group for immunodeficiency) and ESID (european society for immunodeficiencies). Clin Immunol. 1999;93:190–7.PubMedCrossRef
15.
go back to reference Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85.PubMedCrossRef Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85.PubMedCrossRef
16.
go back to reference Malphettes M, Gérard L, Carmagnat M, Mouillot G, Vince N, Boutboul D, et al. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis. 2009;49:1329–38.PubMedCrossRef Malphettes M, Gérard L, Carmagnat M, Mouillot G, Vince N, Boutboul D, et al. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis. 2009;49:1329–38.PubMedCrossRef
17.
go back to reference Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiol. 1990;1:43–6. Rothman KJ. No adjustments are needed for multiple comparisons. Epidemiol. 1990;1:43–6.
18.
go back to reference Perneger TV. What’s wrong with Bonferroni adjustments. BMJ. 1998;316:1236–8. Perneger TV. What’s wrong with Bonferroni adjustments. BMJ. 1998;316:1236–8.
19.
go back to reference Ibanez C, Sune P, Fierro A, Rodriguez S, Lopez M, Alvarez A, et al. Modulating effects of intravenous immunoglobulins on serum cytokine levels in patients with primary hypogammaglobulinemia. Biodrugs. 2005;19:59–65.PubMedCrossRef Ibanez C, Sune P, Fierro A, Rodriguez S, Lopez M, Alvarez A, et al. Modulating effects of intravenous immunoglobulins on serum cytokine levels in patients with primary hypogammaglobulinemia. Biodrugs. 2005;19:59–65.PubMedCrossRef
20.
go back to reference Rezaei N, Aghamohammadi A, Kardar GA, Nourizadeh M, Pourpak Z. T- helper 1 and 2 cytokine assay in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2008;18:449–53.PubMed Rezaei N, Aghamohammadi A, Kardar GA, Nourizadeh M, Pourpak Z. T- helper 1 and 2 cytokine assay in patients with common variable immunodeficiency. J Investig Allergol Clin Immunol. 2008;18:449–53.PubMed
21.
go back to reference Kasztalska K, Ciebiada M, Cebula-Obrzut B, Górski P. Intravenous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency disease: an open-label prospective study. Clin Drug Investig. 2011;31:299–307.PubMedCrossRef Kasztalska K, Ciebiada M, Cebula-Obrzut B, Górski P. Intravenous immunoglobulin replacement therapy in the treatment of patients with common variable immunodeficiency disease: an open-label prospective study. Clin Drug Investig. 2011;31:299–307.PubMedCrossRef
22.
go back to reference Li K, Li NL, Wei D, Pfeffer SR, Fan M, Pfeffer LM. Activation of chemokine and inflammatory cytokine response in hepatitis C virus-infected hepatocytes depends on Toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates. Hepatol. 2012;55:666–75.CrossRef Li K, Li NL, Wei D, Pfeffer SR, Fan M, Pfeffer LM. Activation of chemokine and inflammatory cytokine response in hepatitis C virus-infected hepatocytes depends on Toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates. Hepatol. 2012;55:666–75.CrossRef
23.
24.
go back to reference Gabay C, Porter B, Guenette D, Billir B, Arend WP. Interleukin-4 (IL-4) and IL-13 enhance the effect of IL-1beta on production of IL-1 receptor antagonist by human primary hepatocytes and hepatoma HepG2 cells: differential effect on C-reactive protein production. Blood. 1999;93:1299–307.PubMed Gabay C, Porter B, Guenette D, Billir B, Arend WP. Interleukin-4 (IL-4) and IL-13 enhance the effect of IL-1beta on production of IL-1 receptor antagonist by human primary hepatocytes and hepatoma HepG2 cells: differential effect on C-reactive protein production. Blood. 1999;93:1299–307.PubMed
25.
go back to reference Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669–92.PubMedCrossRef Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669–92.PubMedCrossRef
26.
go back to reference Han J, Wang B, Han N, Zhao Y, Song C, Feng X, et al. CD14 (high) CD16 (+) rather than CD14 (low) CD16 (+) monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr. 2009;52:553–9.PubMedCrossRef Han J, Wang B, Han N, Zhao Y, Song C, Feng X, et al. CD14 (high) CD16 (+) rather than CD14 (low) CD16 (+) monocytes correlate with disease progression in chronic HIV-infected patients. J Acquir Immune Defic Syndr. 2009;52:553–9.PubMedCrossRef
27.
go back to reference Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One. 2008;3:e2516.PubMedCentralPubMedCrossRef Ancuta P, Kamat A, Kunstman KJ, Kim EY, Autissier P, Wurcel A, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PLoS One. 2008;3:e2516.PubMedCentralPubMedCrossRef
28.
go back to reference Amoras AL, da Silva MT, Zollner RL, Kanegane H, Miyawaki T, Vilela MM. Expression of Fc gamma and complement receptors in monocytes of X-linked agammaglobulinaemia and common variable immunodeficiency patients. Clin Exp Immunol. 2007;150:422–8.PubMedCentralPubMedCrossRef Amoras AL, da Silva MT, Zollner RL, Kanegane H, Miyawaki T, Vilela MM. Expression of Fc gamma and complement receptors in monocytes of X-linked agammaglobulinaemia and common variable immunodeficiency patients. Clin Exp Immunol. 2007;150:422–8.PubMedCentralPubMedCrossRef
29.
go back to reference Aukrust P, Müller F, Frøland SS. Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. Clin Immunol Immunopathol. 1994;70:217–24.PubMedCrossRef Aukrust P, Müller F, Frøland SS. Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes. Clin Immunol Immunopathol. 1994;70:217–24.PubMedCrossRef
30.
go back to reference Holm AM, Aukrust P, Damas JK, Muller F, Halvorsen B, Froland SS. Abnormal interleukin-7 function in common variable immunodeficiency. Blood. 2005;105:2887–90.PubMedCrossRef Holm AM, Aukrust P, Damas JK, Muller F, Halvorsen B, Froland SS. Abnormal interleukin-7 function in common variable immunodeficiency. Blood. 2005;105:2887–90.PubMedCrossRef
31.
go back to reference Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21:331–44.PubMedCrossRef Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, et al. Biology of interleukin-10. Cytokine Growth Factor Rev. 2010;21:331–44.PubMedCrossRef
32.
go back to reference Fevang B, Yndestad A, Damås JK, Halvorsen B, Holm AM, Beiske K, et al. Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation. Clin Exp Immunol. 2009;158:237–45.PubMedCentralPubMedCrossRef Fevang B, Yndestad A, Damås JK, Halvorsen B, Holm AM, Beiske K, et al. Chemokines and common variable immunodeficiency; possible contribution of CCL19, CCL21 and CCR7 to immune dysregulation. Clin Exp Immunol. 2009;158:237–45.PubMedCentralPubMedCrossRef
33.
go back to reference Martinez-Pomar N, Raga S, Ferrer J, Pons J, Munoz-Saa I, Julia MR, et al. Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and interferon-gamma gene. Clin Exp Immunol. 2006;144:233–8.PubMedCentralPubMedCrossRef Martinez-Pomar N, Raga S, Ferrer J, Pons J, Munoz-Saa I, Julia MR, et al. Elevated serum interleukin (IL)-12p40 levels in common variable immunodeficiency disease and decreased peripheral blood dendritic cells: analysis of IL-12p40 and interferon-gamma gene. Clin Exp Immunol. 2006;144:233–8.PubMedCentralPubMedCrossRef
34.
go back to reference Cambronero R, Sewell WA, North ME, Webster AD, Farrant J. Up-regulation of IL-12 in monocytes: a fundamental defect in common variable immunodeficiency. J Immunol. 2000;164:488–94.PubMedCrossRef Cambronero R, Sewell WA, North ME, Webster AD, Farrant J. Up-regulation of IL-12 in monocytes: a fundamental defect in common variable immunodeficiency. J Immunol. 2000;164:488–94.PubMedCrossRef
35.
go back to reference Shimozato O, Ugai S, Chiyo M, Takenobu H, Nagakawa H, Wada A, et al. The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects. Immunol. 2006;117:22–8.CrossRef Shimozato O, Ugai S, Chiyo M, Takenobu H, Nagakawa H, Wada A, et al. The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects. Immunol. 2006;117:22–8.CrossRef
36.
go back to reference Schmitt DA, Ullrich SE. Exposure to ultraviolet radiation causes dendritic cells/macrophages to secrete immune-suppressive IL-12p40 homodimers. J Immunol. 2000;165:3162–7.PubMedCrossRef Schmitt DA, Ullrich SE. Exposure to ultraviolet radiation causes dendritic cells/macrophages to secrete immune-suppressive IL-12p40 homodimers. J Immunol. 2000;165:3162–7.PubMedCrossRef
37.
go back to reference Barbosa RR, Silva SP, Silva SL, Melo AC, Pedro E, Barbosa MP, et al. Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation. PLoS One. 2011;6:e22848.PubMedCentralPubMedCrossRef Barbosa RR, Silva SP, Silva SL, Melo AC, Pedro E, Barbosa MP, et al. Primary B-cell deficiencies reveal a link between human IL-17-producing CD4 T-cell homeostasis and B-cell differentiation. PLoS One. 2011;6:e22848.PubMedCentralPubMedCrossRef
38.
go back to reference Reiberger T, Aberle JH, Kundi M, Kohrgruber N, Rieger A, Gangl A, et al. IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection. Antivir Ther. 2008;13:969–76.PubMed Reiberger T, Aberle JH, Kundi M, Kohrgruber N, Rieger A, Gangl A, et al. IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection. Antivir Ther. 2008;13:969–76.PubMed
39.
go back to reference Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, et al. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J Infect Dis. 2006;194:895–903.PubMedCrossRef Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, et al. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection. J Infect Dis. 2006;194:895–903.PubMedCrossRef
40.
go back to reference Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, et al. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C (high) CCR2 (+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011;186:5993–6003.PubMedCentralPubMedCrossRef Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, et al. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C (high) CCR2 (+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011;186:5993–6003.PubMedCentralPubMedCrossRef
41.
go back to reference Ying S, Robinson DS, Meng Q, Barata LT, McEuen AR, Buckley MG, et al. C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (monocyte chemoattractant protein-3 and RANTES). J Immunol. 1999;163:3976–84.PubMed Ying S, Robinson DS, Meng Q, Barata LT, McEuen AR, Buckley MG, et al. C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (monocyte chemoattractant protein-3 and RANTES). J Immunol. 1999;163:3976–84.PubMed
42.
go back to reference Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW. Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells. J Exp Med. 1993;178:1629–36.PubMedCrossRef Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW. Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells. J Exp Med. 1993;178:1629–36.PubMedCrossRef
43.
go back to reference McDonald PP, Gasperini S, Calzetti F, Cassatella MA. Modulation by interferon-gamma of the production and gene expression of IL-1 receptor antagonist in human neutrophils. Cell Immunol. 1998;184:45–50.PubMedCrossRef McDonald PP, Gasperini S, Calzetti F, Cassatella MA. Modulation by interferon-gamma of the production and gene expression of IL-1 receptor antagonist in human neutrophils. Cell Immunol. 1998;184:45–50.PubMedCrossRef
44.
go back to reference Bank U, Reinhold D, Schneemilch C, Kunz D, Synowitz HJ, Ansorge S. Selective proteolytic cleavage of IL-2 receptor and IL-6 receptor ligand binding chains by neutrophil-derived serine proteases at foci of inflammation. J Interferon Cytokine Res. 1999;19:1277–87.PubMedCrossRef Bank U, Reinhold D, Schneemilch C, Kunz D, Synowitz HJ, Ansorge S. Selective proteolytic cleavage of IL-2 receptor and IL-6 receptor ligand binding chains by neutrophil-derived serine proteases at foci of inflammation. J Interferon Cytokine Res. 1999;19:1277–87.PubMedCrossRef
45.
go back to reference Sheu BC, Hsu SM, Ho HN, Lien HC, Huang SC, Lin RH. A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res. 2001;61:237–42.PubMed Sheu BC, Hsu SM, Ho HN, Lien HC, Huang SC, Lin RH. A novel role of metalloproteinase in cancer-mediated immunosuppression. Cancer Res. 2001;61:237–42.PubMed
46.
go back to reference Yang ZZ, Grote DM, Ziesmer SC, Manske MK, Witzig TE, Novak AJ, et al. Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood. 2011;118:2809–20.PubMedCentralPubMedCrossRef Yang ZZ, Grote DM, Ziesmer SC, Manske MK, Witzig TE, Novak AJ, et al. Soluble IL-2Rα facilitates IL-2-mediated immune responses and predicts reduced survival in follicular B-cell non-Hodgkin lymphoma. Blood. 2011;118:2809–20.PubMedCentralPubMedCrossRef
47.
go back to reference Cabrera R, Ararat M, Eksioglu EA, Cao M, Xu Y, Wasserfall C, et al. Influence of serum and soluble CD25 (sCD25) on regulatory and effector T-cell function in hepatocellular carcinoma. Scand J Immunol. 2010;72:293–301.PubMedCentralPubMedCrossRef Cabrera R, Ararat M, Eksioglu EA, Cao M, Xu Y, Wasserfall C, et al. Influence of serum and soluble CD25 (sCD25) on regulatory and effector T-cell function in hepatocellular carcinoma. Scand J Immunol. 2010;72:293–301.PubMedCentralPubMedCrossRef
48.
go back to reference Bien E, Balcerska A. Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. Biomarkers. 2008;13:1–26.PubMedCrossRef Bien E, Balcerska A. Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. Biomarkers. 2008;13:1–26.PubMedCrossRef
49.
go back to reference Downes K, Marcovecchio ML, Clarke P, Cooper JD, Ferreira RC, Howson JM, et al. Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients. Diabetologia. 2014;57:366–72.PubMedCentralPubMedCrossRef Downes K, Marcovecchio ML, Clarke P, Cooper JD, Ferreira RC, Howson JM, et al. Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients. Diabetologia. 2014;57:366–72.PubMedCentralPubMedCrossRef
50.
go back to reference North ME, Spickett GP, Webster AD, Farrant J. Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. Clin Exp Immunol. 1991;86:252–5.PubMedCentralPubMedCrossRef North ME, Spickett GP, Webster AD, Farrant J. Raised serum levels of CD8, CD25 and beta 2-microglobulin in common variable immunodeficiency. Clin Exp Immunol. 1991;86:252–5.PubMedCentralPubMedCrossRef
51.
go back to reference Micol R, Kayal S, Mahlaoui N, Beauté J, Brosselin P, Dudoit Y, et al. Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia. J Allergy Clin Immunol. 2012;129:770–7.PubMedCrossRef Micol R, Kayal S, Mahlaoui N, Beauté J, Brosselin P, Dudoit Y, et al. Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia. J Allergy Clin Immunol. 2012;129:770–7.PubMedCrossRef
Metadata
Title
Altered Serum Cytokine Signature in Common Variable Immunodeficiency
Authors
Zdenek Hel
Richard P. H. Huijbregts
Jun Xu
Jana Nechvatalova
Marcela Vlkova
Jiri Litzman
Publication date
01-11-2014
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 8/2014
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-014-0099-z

Other articles of this Issue 8/2014

Journal of Clinical Immunology 8/2014 Go to the issue