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CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease
Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700691/ https://www.ncbi.nlm.nih.gov/pubmed/36433996 http://dx.doi.org/10.1038/s41467-022-34873-7 |
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author | Pierson, Sheila K. Katz, Laura Williams, Reece Mumau, Melanie Gonzalez, Michael Guzman, Stacy Rubenstein, Ayelet Oromendia, Ana B. Beineke, Philip Fosså, Alexander van Rhee, Frits Fajgenbaum, David C. |
author_facet | Pierson, Sheila K. Katz, Laura Williams, Reece Mumau, Melanie Gonzalez, Michael Guzman, Stacy Rubenstein, Ayelet Oromendia, Ana B. Beineke, Philip Fosså, Alexander van Rhee, Frits Fajgenbaum, David C. |
author_sort | Pierson, Sheila K. |
collection | PubMed |
description | Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD. |
format | Online Article Text |
id | pubmed-9700691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97006912022-11-27 CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease Pierson, Sheila K. Katz, Laura Williams, Reece Mumau, Melanie Gonzalez, Michael Guzman, Stacy Rubenstein, Ayelet Oromendia, Ana B. Beineke, Philip Fosså, Alexander van Rhee, Frits Fajgenbaum, David C. Nat Commun Article Idiopathic multicentric Castleman disease (iMCD) is a rare and poorly-understood cytokine storm-driven inflammatory disorder. Interleukin-6 (IL-6) is a known disease driver in some patients, but anti-IL-6 therapy with siltuximab is not effective in all patients, and biomarkers indicating success at an early time point following treatment initiation are lacking. Here we show, by comparison of levels of 1,178 proteins in sera of healthy participants (N = 42), patients with iMCD (N = 88), and with related diseases (N = 60), a comprehensive landscape of candidate disease mediators and predictors of siltuximab response. C-X-C Motif Chemokine Ligand-13 (CXCL13) is identified and validated as the protein most prominently up-regulated in iMCD. Early and significant decrease in CXCL13 levels clearly distinguishes siltuximab responders from non-responders; a 17% reduction by day 8 following siltuximab therapy initiation is predictive of response at later time points. Our study thus suggests that CXCL13 is a predictive biomarker of response to siltuximab in iMCD. Nature Publishing Group UK 2022-11-24 /pmc/articles/PMC9700691/ /pubmed/36433996 http://dx.doi.org/10.1038/s41467-022-34873-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pierson, Sheila K. Katz, Laura Williams, Reece Mumau, Melanie Gonzalez, Michael Guzman, Stacy Rubenstein, Ayelet Oromendia, Ana B. Beineke, Philip Fosså, Alexander van Rhee, Frits Fajgenbaum, David C. CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title | CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title_full | CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title_fullStr | CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title_full_unstemmed | CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title_short | CXCL13 is a predictive biomarker in idiopathic multicentric Castleman disease |
title_sort | cxcl13 is a predictive biomarker in idiopathic multicentric castleman disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9700691/ https://www.ncbi.nlm.nih.gov/pubmed/36433996 http://dx.doi.org/10.1038/s41467-022-34873-7 |
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