Bronchial epithelial cell transcriptome shows endotype heterogeneity of asthma in patients with NSAID-exacerbated respiratory disease - 05/04/23
, Jerzy Soja, MD, PhD a, Krzysztof Sladek, MD, PhD a, Marek Przybyszowski, MD, PhD a, Hanna Plutecka, PhD a, Anna Gielicz, MSc a, Sabina Licholai, MD a, Alar Aab, PhD b, Ana Rebane, PhD b, Grazyna Bochenek, MD, PhD a, ⁎ Abstract |
Background |
Nonsteroidal anti-inflammatory drugs–exacerbated respiratory disease (N-ERD) is currently classified as a type-2 (T2) immune-mediated disease characterized by asthma, chronic rhinosinusitis, and hypersensitivity to cyclooxygenase-1 inhibitors.
Objectives |
The aim of this study was to characterize immunological endotypes of N-ERD based on the gene expression profile in the bronchial epithelium.
Methods |
mRNA transcriptome (mRNA-sequencing) was analyzed in bronchial brushings from patients with N-ERD (n = 22), those with nonsteroidal anti-inflammatory drug–tolerant asthma (NTA, n = 21), and control subjects (n = 11). Additionally, lipid and protein mediators were measured in bronchoalveolar lavage fluid (BALF).
Results |
Initial analysis of the entire asthma group revealed 2 distinct gene expression signatures: “T2-high” with increased expression of T2-related genes (eg, CLCA1, CST1), and “proinflammatory” characterized by the expression of innate immunity (eg, FOSB, EGR3) and IL-17A response genes. These endotypes showed similar prevalence in N-ERD and NTA (eg, T2-high: 33% and 32%, respectively). T2-high asthma was characterized by increased expression of mast cell and eosinophil markers, goblet cell hyperplasia, and elevated LTE4 and PGD2 in BALF. Patients with a proinflammatory endotype showed mainly neutrophilic inflammation and increased innate immunity mediators in BALF. Furthermore, the proinflammatory signature was associated with a more severe course of asthma and marked airway obstruction. These signatures could be recreated in vitro by exposure of bronchial epithelial cells to IL-13 (T2-high) and IL-17A (proinflammatory).
Conclusions |
T2-high signature was found only in one-third of patients with N-ERD, which was similar to what was found in patients with NTA. The proinflammatory endotype, which also occurred in N-ERD, suggests a novel mechanism of severe disease developing on a non-T2 background.
El texto completo de este artículo está disponible en PDF.Key words : Asthma, NSAID–exacerbated respiratory disease, asthma endotypes, bronchial epithelium, gene expression
Abbreviations used : BALF, cysLTs, DEG, HBECs, N-ERD, NSAIDs, NTA, PNEC, qPCR, T2
Esquema
| Supported by the Polish National Science Center (grants UMO-2014/15/B/NZ5/01539 [to G.B.] and UMO-2014/13/B/NZ3/02393 [to B.J.]). A.R. was supported by a personal research grant (PRG1259) from the Estonian Research Council. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 4
P. 953-965 - avril 2023 Regresar al número
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