Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.

<h4>Background</h4>Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune resp...

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Autores principales:	Marzia Dolcino, Giuseppe Patuzzo, Alessandro Barbieri, Elisa Tinazzi, Monica Rizzi, Ruggero Beri, Giuseppe Argentino, Andrea Ottria, Claudio Lunardi, Antonio Puccetti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d9ef2abdd8342708dac08ddc6ba3042
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spelling	oai:doaj.org-article:1d9ef2abdd8342708dac08ddc6ba30422021-11-18T08:19:05ZGene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.1932-620310.1371/journal.pone.0097571https://doaj.org/article/1d9ef2abdd8342708dac08ddc6ba30422014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24831519/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice.<h4>Methods</h4>We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study.<h4>Results</h4>A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes).<h4>Conclusions</h4>Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.Marzia DolcinoGiuseppe PatuzzoAlessandro BarbieriElisa TinazziMonica RizziRuggero BeriGiuseppe ArgentinoAndrea OttriaClaudio LunardiAntonio PuccettiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e97571 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marzia Dolcino Giuseppe Patuzzo Alessandro Barbieri Elisa Tinazzi Monica Rizzi Ruggero Beri Giuseppe Argentino Andrea Ottria Claudio Lunardi Antonio Puccetti Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
description	<h4>Background</h4>Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice.<h4>Methods</h4>We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study.<h4>Results</h4>A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23⁻CD27⁻IgM⁻IgG⁻ B cells (centrocytes).<h4>Conclusions</h4>Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency.
format	article
author	Marzia Dolcino Giuseppe Patuzzo Alessandro Barbieri Elisa Tinazzi Monica Rizzi Ruggero Beri Giuseppe Argentino Andrea Ottria Claudio Lunardi Antonio Puccetti
author_facet	Marzia Dolcino Giuseppe Patuzzo Alessandro Barbieri Elisa Tinazzi Monica Rizzi Ruggero Beri Giuseppe Argentino Andrea Ottria Claudio Lunardi Antonio Puccetti
author_sort	Marzia Dolcino
title	Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
title_short	Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
title_full	Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
title_fullStr	Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
title_full_unstemmed	Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
title_sort	gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/1d9ef2abdd8342708dac08ddc6ba3042
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Gene expression profiling in peripheral blood mononuclear cells of patients with common variable immunodeficiency: modulation of adaptive immune response following intravenous immunoglobulin therapy.

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