Airway gene expression identifies subtypes of type 2 inflammation in severe asthma

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Airway gene expression identifies subtypes of type 2 inflammation in severe asthma. / Frøssing, Laurits; Silberbrandt, Alexander; Von Bülow, Anna; Kjærsgaard Klein, Ditte; Ross Christensen, Marcus; Backer, Vibeke; Baines, Katherine J.; Porsbjerg, Celeste.

I: Clinical and Experimental Allergy, Bind 52, Nr. 1, 2022, s. 59-69.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Frøssing, L, Silberbrandt, A, Von Bülow, A, Kjærsgaard Klein, D, Ross Christensen, M, Backer, V, Baines, KJ & Porsbjerg, C 2022, 'Airway gene expression identifies subtypes of type 2 inflammation in severe asthma', Clinical and Experimental Allergy, bind 52, nr. 1, s. 59-69. https://doi.org/10.1111/cea.13966

APA

Frøssing, L., Silberbrandt, A., Von Bülow, A., Kjærsgaard Klein, D., Ross Christensen, M., Backer, V., Baines, K. J., & Porsbjerg, C. (2022). Airway gene expression identifies subtypes of type 2 inflammation in severe asthma. Clinical and Experimental Allergy, 52(1), 59-69. https://doi.org/10.1111/cea.13966

Vancouver

Frøssing L, Silberbrandt A, Von Bülow A, Kjærsgaard Klein D, Ross Christensen M, Backer V o.a. Airway gene expression identifies subtypes of type 2 inflammation in severe asthma. Clinical and Experimental Allergy. 2022;52(1):59-69. https://doi.org/10.1111/cea.13966

Author

Frøssing, Laurits ; Silberbrandt, Alexander ; Von Bülow, Anna ; Kjærsgaard Klein, Ditte ; Ross Christensen, Marcus ; Backer, Vibeke ; Baines, Katherine J. ; Porsbjerg, Celeste. / Airway gene expression identifies subtypes of type 2 inflammation in severe asthma. I: Clinical and Experimental Allergy. 2022 ; Bind 52, Nr. 1. s. 59-69.

Bibtex

@article{187ef28ac5a34bc9b7ae9a9d67e8af7c,

title = "Airway gene expression identifies subtypes of type 2 inflammation in severe asthma",

abstract = "Background: Type 2 inflammation is characterized by enhanced activity of interleukin (IL)-4, -5 and -13, and treatments targeting these pathways are available for treatment of severe asthma. At present, the pattern of pathway activity and the implications overlapping of pathway activity are unknown. Objective: We hypothesized that clustering of airway mRNA expression would identify distinct molecular subtypes of severe asthma and thereby uncover the prevalence and overlap of pathway activity. Methods: Sputum mRNA expression of genes related to expression of IL-5(CLC, CPA3 and DNASE1L3), IL-13(IL13Ra1, TNFSF14 and SERPINB2), T1/Th17 activity(IL1B, ALPL and CXCR2) and in vitro response to corticosteroids (FKBP512) and mepolizumab (ARAP3) was analysed in patients (n = 109) with severe asthma and healthy controls (n = 22). A cluster analysis of gene expression was performed. The response to a short course of OCS was assessed in a subset of patients (n = 29). Results: Five molecular clusters were identified. Three had abundant T2 gene expression of which two (n = 39 and n = 9) were characterized by abundant expression of both IL-13- and IL-5-related genes. The last (n = 6) had only abundant IL-5-related gene expression. These T2-high molecular clusters could not be distinguished using T2 biomarkers. T2- and Th1/Th17-related mRNA expression were co-expressed across all clusters. OCS significantly reduced T2 gene expression (CLC, IL13Ra1, SERPINB2 and ARAP3) and significantly increase expression of Th1/Th17-related genes (ALPL and CXCR2). Conclusions and clinical relevance: Clustering of airway mRNA expression identified five molecular clusters of severe asthma of which three were considered T2 high. Co-expression of IL-5- and IL-13-related genes at moderate levels was present in almost half of patients, while marked elevated expression of both was rare. In contrast to IL-5, clusters with isolated IL-13- and Th1/Th17-related gene expression were not identified.",

author = "Laurits Fr{\o}ssing and Alexander Silberbrandt and {Von B{\"u}low}, Anna and {Kj{\ae}rsgaard Klein}, Ditte and {Ross Christensen}, Marcus and Vibeke Backer and Baines, {Katherine J.} and Celeste Porsbjerg",

note = "Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons Ltd.",

year = "2022",

doi = "10.1111/cea.13966",

language = "English",

volume = "52",

pages = "59--69",

journal = "Clinical Allergy",

issn = "0954-7894",

publisher = "Wiley-Blackwell",

number = "1",

}

RIS

TY - JOUR

T1 - Airway gene expression identifies subtypes of type 2 inflammation in severe asthma

AU - Frøssing, Laurits

AU - Silberbrandt, Alexander

AU - Von Bülow, Anna

AU - Kjærsgaard Klein, Ditte

AU - Ross Christensen, Marcus

AU - Backer, Vibeke

AU - Baines, Katherine J.

AU - Porsbjerg, Celeste

PY - 2022

Y1 - 2022

N2 - Background: Type 2 inflammation is characterized by enhanced activity of interleukin (IL)-4, -5 and -13, and treatments targeting these pathways are available for treatment of severe asthma. At present, the pattern of pathway activity and the implications overlapping of pathway activity are unknown. Objective: We hypothesized that clustering of airway mRNA expression would identify distinct molecular subtypes of severe asthma and thereby uncover the prevalence and overlap of pathway activity. Methods: Sputum mRNA expression of genes related to expression of IL-5(CLC, CPA3 and DNASE1L3), IL-13(IL13Ra1, TNFSF14 and SERPINB2), T1/Th17 activity(IL1B, ALPL and CXCR2) and in vitro response to corticosteroids (FKBP512) and mepolizumab (ARAP3) was analysed in patients (n = 109) with severe asthma and healthy controls (n = 22). A cluster analysis of gene expression was performed. The response to a short course of OCS was assessed in a subset of patients (n = 29). Results: Five molecular clusters were identified. Three had abundant T2 gene expression of which two (n = 39 and n = 9) were characterized by abundant expression of both IL-13- and IL-5-related genes. The last (n = 6) had only abundant IL-5-related gene expression. These T2-high molecular clusters could not be distinguished using T2 biomarkers. T2- and Th1/Th17-related mRNA expression were co-expressed across all clusters. OCS significantly reduced T2 gene expression (CLC, IL13Ra1, SERPINB2 and ARAP3) and significantly increase expression of Th1/Th17-related genes (ALPL and CXCR2). Conclusions and clinical relevance: Clustering of airway mRNA expression identified five molecular clusters of severe asthma of which three were considered T2 high. Co-expression of IL-5- and IL-13-related genes at moderate levels was present in almost half of patients, while marked elevated expression of both was rare. In contrast to IL-5, clusters with isolated IL-13- and Th1/Th17-related gene expression were not identified.

AB - Background: Type 2 inflammation is characterized by enhanced activity of interleukin (IL)-4, -5 and -13, and treatments targeting these pathways are available for treatment of severe asthma. At present, the pattern of pathway activity and the implications overlapping of pathway activity are unknown. Objective: We hypothesized that clustering of airway mRNA expression would identify distinct molecular subtypes of severe asthma and thereby uncover the prevalence and overlap of pathway activity. Methods: Sputum mRNA expression of genes related to expression of IL-5(CLC, CPA3 and DNASE1L3), IL-13(IL13Ra1, TNFSF14 and SERPINB2), T1/Th17 activity(IL1B, ALPL and CXCR2) and in vitro response to corticosteroids (FKBP512) and mepolizumab (ARAP3) was analysed in patients (n = 109) with severe asthma and healthy controls (n = 22). A cluster analysis of gene expression was performed. The response to a short course of OCS was assessed in a subset of patients (n = 29). Results: Five molecular clusters were identified. Three had abundant T2 gene expression of which two (n = 39 and n = 9) were characterized by abundant expression of both IL-13- and IL-5-related genes. The last (n = 6) had only abundant IL-5-related gene expression. These T2-high molecular clusters could not be distinguished using T2 biomarkers. T2- and Th1/Th17-related mRNA expression were co-expressed across all clusters. OCS significantly reduced T2 gene expression (CLC, IL13Ra1, SERPINB2 and ARAP3) and significantly increase expression of Th1/Th17-related genes (ALPL and CXCR2). Conclusions and clinical relevance: Clustering of airway mRNA expression identified five molecular clusters of severe asthma of which three were considered T2 high. Co-expression of IL-5- and IL-13-related genes at moderate levels was present in almost half of patients, while marked elevated expression of both was rare. In contrast to IL-5, clusters with isolated IL-13- and Th1/Th17-related gene expression were not identified.

U2 - 10.1111/cea.13966

DO - 10.1111/cea.13966

M3 - Journal article

C2 - 34142396

AN - SCOPUS:85108826435

VL - 52

SP - 59

EP - 69

JO - Clinical Allergy

JF - Clinical Allergy

SN - 0954-7894

IS - 1

ER -

ID: 314154457