Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Abstract Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patient...

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Autores principales:	Ana Colado, Esteban Enrique Elías, Valeria Judith Sarapura Martínez, Gregorio Cordini, Pablo Morande, Fernando Bezares, Mirta Giordano, Romina Gamberale, Mercedes Borge
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/228884abb3ea4cbb9bf9765125f589ab
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spelling	oai:doaj.org-article:228884abb3ea4cbb9bf9765125f589ab2021-12-02T17:12:25ZImmunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia10.1038/s41598-021-92412-82045-2322https://doaj.org/article/228884abb3ea4cbb9bf9765125f589ab2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92412-8https://doaj.org/toc/2045-2322Abstract Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.Ana ColadoEsteban Enrique ElíasValeria Judith Sarapura MartínezGregorio CordiniPablo MorandeFernando BezaresMirta GiordanoRomina GamberaleMercedes BorgeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Colado Esteban Enrique Elías Valeria Judith Sarapura Martínez Gregorio Cordini Pablo Morande Fernando Bezares Mirta Giordano Romina Gamberale Mercedes Borge Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
description	Abstract Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.
format	article
author	Ana Colado Esteban Enrique Elías Valeria Judith Sarapura Martínez Gregorio Cordini Pablo Morande Fernando Bezares Mirta Giordano Romina Gamberale Mercedes Borge
author_facet	Ana Colado Esteban Enrique Elías Valeria Judith Sarapura Martínez Gregorio Cordini Pablo Morande Fernando Bezares Mirta Giordano Romina Gamberale Mercedes Borge
author_sort	Ana Colado
title	Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
title_short	Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
title_full	Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
title_fullStr	Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
title_full_unstemmed	Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
title_sort	immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/228884abb3ea4cbb9bf9765125f589ab
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Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

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