A Nasal Inflammatory Cytokine Signature Is Associated with Early Graft-versus-Host Disease of the Lung after Allogeneic Hematopoietic Cell Transplantation: Proof of Concept

Authors

Edwin J Ostrin
Nicholas L Rider
Amin M Alousi
Ehsan Irajizad
Liang Li
Qian Peng
Sang T Kim
Lara Bashoura
Muhammad H Arain
Laila Z Noor
Nikul Patel
Rohtesh Mehta
Uday R Popat
Chitra Hosing
Robert R Jenq
Gabriela Rondon
Samir M Hanash
Sophie Paczesny
Elizabeth J Shpall
Richard E Champlin
Burton F Dickey
Ajay Sheshadri

Publication Date

6-1-2023

Journal

Immunohorizons

Abstract

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.

Keywords

Humans, Cytokines, Bronchiolitis Obliterans, Lung Transplantation, Lung, Graft vs Host Disease, Inflammation, Bronchiolitis Obliterans Syndrome, Hematopoietic Stem Cell Transplantation

Comments

Supplementary Materials

PMID: 37289498