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A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept
Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particul...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AAI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491477/ https://www.ncbi.nlm.nih.gov/pubmed/37289498 http://dx.doi.org/10.4049/immunohorizons.2300031 |
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author | Ostrin, Edwin J. Rider, Nicholas L. Alousi, Amin M. Irajizad, Ehsan Li, Liang Peng, Qian Kim, Sang T. Bashoura, Lara Arain, Muhammad H. Noor, Laila Z. Patel, Nikul Mehta, Rohtesh Popat, Uday R. Hosing, Chitra Jenq, Robert R. Rondon, Gabriela Hanash, Samir M. Paczesny, Sophie Shpall, Elizabeth J. Champlin, Richard E. Dickey, Burton F. Sheshadri, Ajay |
author_facet | Ostrin, Edwin J. Rider, Nicholas L. Alousi, Amin M. Irajizad, Ehsan Li, Liang Peng, Qian Kim, Sang T. Bashoura, Lara Arain, Muhammad H. Noor, Laila Z. Patel, Nikul Mehta, Rohtesh Popat, Uday R. Hosing, Chitra Jenq, Robert R. Rondon, Gabriela Hanash, Samir M. Paczesny, Sophie Shpall, Elizabeth J. Champlin, Richard E. Dickey, Burton F. Sheshadri, Ajay |
author_sort | Ostrin, Edwin J. |
collection | PubMed |
description | Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particularly early BOS. We conducted a prospective observational study in HCT recipients with new-onset BOS (n = 14), BOS stage 0p (n = 10), and recipients without lung impairment with (n = 3) or without (n = 8) chronic graft-versus-host disease and measured nasal inflammation using nasosorption at enrollment and then every 3 mo for 1 y. We divided BOS stage 0p into impairment that did not return to baseline values (preBOS, n = 6), or transient impairment (n = 4). We tested eluted nasal mucosal lining fluid from nasosorption matrices for inflammatory chemokines and cytokines using multiplex magnetic bead immunoassays. We analyzed between-group differences using the Kruskal–Wallis method, adjusting for multiple comparisons. We found increased nasal inflammation in preBOS and therefore directly compared patients with preBOS to those with transient impairment, as this would be of greatest diagnostic relevance. After adjusting for multiple corrections, we found significant increases in growth factors (FGF2, TGF-α, GM-CSF, VEGF), macrophage activation (CCL4, TNF-α, IL-6), neutrophil activation (CXCL2, IL-8), T cell activation (CD40 ligand, IL-2, IL-12p70, IL-15), type 2 inflammation (eotaxin, IL-4, IL-13), type 17 inflammation (IL-17A), dendritic maturation (FLT3 ligand, IL-7), and counterregulatory molecules (PD-L1, IL-1 receptor antagonist, IL-10) in preBOS patients compared to transient impairment. These differences waned over time. In conclusion, a transient multifaceted nasal inflammatory response is associated with preBOS. Our findings require validation in larger longitudinal cohorts. |
format | Online Article Text |
id | pubmed-10491477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | AAI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104914772023-09-08 A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept Ostrin, Edwin J. Rider, Nicholas L. Alousi, Amin M. Irajizad, Ehsan Li, Liang Peng, Qian Kim, Sang T. Bashoura, Lara Arain, Muhammad H. Noor, Laila Z. Patel, Nikul Mehta, Rohtesh Popat, Uday R. Hosing, Chitra Jenq, Robert R. Rondon, Gabriela Hanash, Samir M. Paczesny, Sophie Shpall, Elizabeth J. Champlin, Richard E. Dickey, Burton F. Sheshadri, Ajay Immunohorizons Adaptive Immunity Respiratory inflammation in bronchiolitis obliterans syndrome (BOS) after hematopoietic cell transplantation (HCT) is poorly understood. Clinical criteria for early-stage BOS (stage 0p) often capture HCT recipients without BOS. Measuring respiratory tract inflammation may help identify BOS, particularly early BOS. We conducted a prospective observational study in HCT recipients with new-onset BOS (n = 14), BOS stage 0p (n = 10), and recipients without lung impairment with (n = 3) or without (n = 8) chronic graft-versus-host disease and measured nasal inflammation using nasosorption at enrollment and then every 3 mo for 1 y. We divided BOS stage 0p into impairment that did not return to baseline values (preBOS, n = 6), or transient impairment (n = 4). We tested eluted nasal mucosal lining fluid from nasosorption matrices for inflammatory chemokines and cytokines using multiplex magnetic bead immunoassays. We analyzed between-group differences using the Kruskal–Wallis method, adjusting for multiple comparisons. We found increased nasal inflammation in preBOS and therefore directly compared patients with preBOS to those with transient impairment, as this would be of greatest diagnostic relevance. After adjusting for multiple corrections, we found significant increases in growth factors (FGF2, TGF-α, GM-CSF, VEGF), macrophage activation (CCL4, TNF-α, IL-6), neutrophil activation (CXCL2, IL-8), T cell activation (CD40 ligand, IL-2, IL-12p70, IL-15), type 2 inflammation (eotaxin, IL-4, IL-13), type 17 inflammation (IL-17A), dendritic maturation (FLT3 ligand, IL-7), and counterregulatory molecules (PD-L1, IL-1 receptor antagonist, IL-10) in preBOS patients compared to transient impairment. These differences waned over time. In conclusion, a transient multifaceted nasal inflammatory response is associated with preBOS. Our findings require validation in larger longitudinal cohorts. AAI 2023-06-08 /pmc/articles/PMC10491477/ /pubmed/37289498 http://dx.doi.org/10.4049/immunohorizons.2300031 Text en Copyright © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Adaptive Immunity Ostrin, Edwin J. Rider, Nicholas L. Alousi, Amin M. Irajizad, Ehsan Li, Liang Peng, Qian Kim, Sang T. Bashoura, Lara Arain, Muhammad H. Noor, Laila Z. Patel, Nikul Mehta, Rohtesh Popat, Uday R. Hosing, Chitra Jenq, Robert R. Rondon, Gabriela Hanash, Samir M. Paczesny, Sophie Shpall, Elizabeth J. Champlin, Richard E. Dickey, Burton F. Sheshadri, Ajay A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title | A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title_full | A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title_fullStr | A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title_full_unstemmed | A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title_short | A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept |
title_sort | nasal inflammatory cytokine signature is associated with early graft-versus-host disease of the lung after allogeneic hematopoietic cell transplantation: proof of concept |
topic | Adaptive Immunity |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491477/ https://www.ncbi.nlm.nih.gov/pubmed/37289498 http://dx.doi.org/10.4049/immunohorizons.2300031 |
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