Long‐term B cell depletion associates with regeneration of kidney function

Abstract Background Chronic kidney disease (CKD) is a common condition that increases mortality and the risk of cardiovascular and other morbidities regardless of underlying renal condition. Chronic inflammation promotes renal fibrosis. Recently, renal B cell infiltrates were described in chronic ki...

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Autores principales:	Susanne V. Fleig, Franz F. Konen, Christoph Schröder, Jessica Schmitz, Stefan Gingele, Jan H. Bräsen, Svjetlana Lovric, Bernhard M. W. Schmidt, Hermann Haller, Thomas Skripuletz, Sibylle vonVietinghoff
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cancer cell migration liver/hepatocytes Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/04b168f3baf14dcbb637959db0b05326
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spelling	oai:doaj.org-article:04b168f3baf14dcbb637959db0b053262021-11-12T19:57:15ZLong‐term B cell depletion associates with regeneration of kidney function2050-452710.1002/iid3.499https://doaj.org/article/04b168f3baf14dcbb637959db0b053262021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.499https://doaj.org/toc/2050-4527Abstract Background Chronic kidney disease (CKD) is a common condition that increases mortality and the risk of cardiovascular and other morbidities regardless of underlying renal condition. Chronic inflammation promotes renal fibrosis. Recently, renal B cell infiltrates were described in chronic kidney disease of various etiologies beyond autoimmunity. Methods We here investigated B cells and indicators of tertiary lymphoid structure formation in human renal biopsies. Renal function was studied during long‐term B cell depletion in human patients with membranous nephropathy and with CKD of unknown origin. Results Cytokine profiles of tertiary lymphoid structure formation were detected in human renal interstitium in a range of kidney diseases. Complex B cell structures consistent with tertiary lymphoid organ formation were evident in human membranous nephropathy. Here, B cell density did not significantly associate with proteinuria severity, but with worse excretory renal function. Proteinuria responses mostly occurred within the first 6 months of B cell depletion. In contrast, recovery of excretory kidney function was observed only after 18 months of continuous therapy, consistent with a structural process. Renal tertiary lymphatic structures were also detected in the absence of autoimmune kidney disease. To start to address whether B cell depletion may affect CKD in a broader population, we assessed kidney function in neurologic patients with CKD of unknown origin. In this cohort, eGFR significantly increased within 24 months of B cell depletion. Conclusion Long‐term B cell depletion associated with significant improvement of excretory kidney function in human CKD. Kinetics and mechanisms of renal B cell aggregation should be investigated further to stratify the impact of B cells and their aggregates as therapeutic targets.Susanne V. FleigFranz F. KonenChristoph SchröderJessica SchmitzStefan GingeleJan H. BräsenSvjetlana LovricBernhard M. W. SchmidtHermann HallerThomas SkripuletzSibylle vonVietinghoffWileyarticlecancercell migrationliver/hepatocytesImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1479-1488 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer cell migration liver/hepatocytes Immunologic diseases. Allergy RC581-607
spellingShingle	cancer cell migration liver/hepatocytes Immunologic diseases. Allergy RC581-607 Susanne V. Fleig Franz F. Konen Christoph Schröder Jessica Schmitz Stefan Gingele Jan H. Bräsen Svjetlana Lovric Bernhard M. W. Schmidt Hermann Haller Thomas Skripuletz Sibylle vonVietinghoff Long‐term B cell depletion associates with regeneration of kidney function
description	Abstract Background Chronic kidney disease (CKD) is a common condition that increases mortality and the risk of cardiovascular and other morbidities regardless of underlying renal condition. Chronic inflammation promotes renal fibrosis. Recently, renal B cell infiltrates were described in chronic kidney disease of various etiologies beyond autoimmunity. Methods We here investigated B cells and indicators of tertiary lymphoid structure formation in human renal biopsies. Renal function was studied during long‐term B cell depletion in human patients with membranous nephropathy and with CKD of unknown origin. Results Cytokine profiles of tertiary lymphoid structure formation were detected in human renal interstitium in a range of kidney diseases. Complex B cell structures consistent with tertiary lymphoid organ formation were evident in human membranous nephropathy. Here, B cell density did not significantly associate with proteinuria severity, but with worse excretory renal function. Proteinuria responses mostly occurred within the first 6 months of B cell depletion. In contrast, recovery of excretory kidney function was observed only after 18 months of continuous therapy, consistent with a structural process. Renal tertiary lymphatic structures were also detected in the absence of autoimmune kidney disease. To start to address whether B cell depletion may affect CKD in a broader population, we assessed kidney function in neurologic patients with CKD of unknown origin. In this cohort, eGFR significantly increased within 24 months of B cell depletion. Conclusion Long‐term B cell depletion associated with significant improvement of excretory kidney function in human CKD. Kinetics and mechanisms of renal B cell aggregation should be investigated further to stratify the impact of B cells and their aggregates as therapeutic targets.
format	article
author	Susanne V. Fleig Franz F. Konen Christoph Schröder Jessica Schmitz Stefan Gingele Jan H. Bräsen Svjetlana Lovric Bernhard M. W. Schmidt Hermann Haller Thomas Skripuletz Sibylle vonVietinghoff
author_facet	Susanne V. Fleig Franz F. Konen Christoph Schröder Jessica Schmitz Stefan Gingele Jan H. Bräsen Svjetlana Lovric Bernhard M. W. Schmidt Hermann Haller Thomas Skripuletz Sibylle vonVietinghoff
author_sort	Susanne V. Fleig
title	Long‐term B cell depletion associates with regeneration of kidney function
title_short	Long‐term B cell depletion associates with regeneration of kidney function
title_full	Long‐term B cell depletion associates with regeneration of kidney function
title_fullStr	Long‐term B cell depletion associates with regeneration of kidney function
title_full_unstemmed	Long‐term B cell depletion associates with regeneration of kidney function
title_sort	long‐term b cell depletion associates with regeneration of kidney function
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/04b168f3baf14dcbb637959db0b05326
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Long‐term B cell depletion associates with regeneration of kidney function

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