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A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells

The TNF family cytokines B‐cell activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR‐Fc) or BAFF and APRIL (TACI‐Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (S...

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Autores principales: Haselmayer, Philipp, Vigolo, Michele, Nys, Josquin, Schneider, Pascal, Hess, Henry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518279/
https://www.ncbi.nlm.nih.gov/pubmed/28383107
http://dx.doi.org/10.1002/eji.201746934
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author Haselmayer, Philipp
Vigolo, Michele
Nys, Josquin
Schneider, Pascal
Hess, Henry
author_facet Haselmayer, Philipp
Vigolo, Michele
Nys, Josquin
Schneider, Pascal
Hess, Henry
author_sort Haselmayer, Philipp
collection PubMed
description The TNF family cytokines B‐cell activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR‐Fc) or BAFF and APRIL (TACI‐Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI‐Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies. TACI‐Fc prevented renal damage during a 12‐week treatment period regardless of autoantibody levels, while BAFFR‐Fc did not despite a similar BAFF‐blocking activity in vivo. TACI‐Fc also decreased established plasma cells in a T‐dependent hapten/carrier immunization system better than single inhibitors of BAFF or APRIL, and sometimes better than combined single inhibitors with at least equivalent BAFF and APRIL inhibitory activities. These results indicate that TACI‐Fc can prevent symptoms of renal damage in a mouse model of SLE when BAFFR‐Fc cannot, and point to a plasticity of plasma cells for survival factors. Targeting plasma cells with TACI‐Fc might be beneficial to prevent autoantibody‐mediated damages in SLE.
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spelling pubmed-55182792017-08-03 A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells Haselmayer, Philipp Vigolo, Michele Nys, Josquin Schneider, Pascal Hess, Henry Eur J Immunol Immunodeficiencies and autoimmunity The TNF family cytokines B‐cell activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR‐Fc) or BAFF and APRIL (TACI‐Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI‐Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies. TACI‐Fc prevented renal damage during a 12‐week treatment period regardless of autoantibody levels, while BAFFR‐Fc did not despite a similar BAFF‐blocking activity in vivo. TACI‐Fc also decreased established plasma cells in a T‐dependent hapten/carrier immunization system better than single inhibitors of BAFF or APRIL, and sometimes better than combined single inhibitors with at least equivalent BAFF and APRIL inhibitory activities. These results indicate that TACI‐Fc can prevent symptoms of renal damage in a mouse model of SLE when BAFFR‐Fc cannot, and point to a plasticity of plasma cells for survival factors. Targeting plasma cells with TACI‐Fc might be beneficial to prevent autoantibody‐mediated damages in SLE. John Wiley and Sons Inc. 2017-04-24 2017-06 /pmc/articles/PMC5518279/ /pubmed/28383107 http://dx.doi.org/10.1002/eji.201746934 Text en © 2017 The Authors. European Journal of Immunology published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Immunodeficiencies and autoimmunity
Haselmayer, Philipp
Vigolo, Michele
Nys, Josquin
Schneider, Pascal
Hess, Henry
A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title_full A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title_fullStr A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title_full_unstemmed A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title_short A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells
title_sort mouse model of systemic lupus erythematosus responds better to soluble taci than to soluble baffr, correlating with depletion of plasma cells
topic Immunodeficiencies and autoimmunity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518279/
https://www.ncbi.nlm.nih.gov/pubmed/28383107
http://dx.doi.org/10.1002/eji.201746934
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