Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab.
Clin Exp Allergy
; 50(9): 1017-1034, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32472607
ABSTRACT
BACKGROUND:
Anti-IgE (omalizumab) has been used for the treatment of moderate-to-severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits.OBJECTIVE:
To investigate the transcriptional variations between omalizumab responders and non-responders and to study the mechanisms of action of omalizumab.METHODS:
The whole blood transcriptomes of moderate-to-severe adult asthma patients (N = 4534 responders and 11 non-responders) were analysed over the course of omalizumab treatment. Non-asthmatic healthy controls (N = 17) were used as controls.RESULTS:
Transcriptome variations between responders and non-responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non-responders tend to remain more similar to their pre-treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up-regulated in non-responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non-responders. CONCLUSION AND CLINICAL RELEVANCE This study provides not only transcriptional variations between omalizumab responders and non-responders, but also molecular insights for controlling asthma by omalizumab.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Antiasmáticos
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Perfilação da Expressão Gênica
/
Transcriptoma
/
Omalizumab
/
Pulmão
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Exp Allergy
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos