Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab.

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 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=45: 34 responders and 11 non-responders) were analyzed 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 genes significant (FDR<0.05) in at least one comparison of each patient response status and time point compared to 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 upregulated 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 & CLINICAL RELEVANCE This study provides not only transcriptional variations between omalizumab responders and non-responders, but also molecular insights for controlling asthma by omalizumab.