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Published on: February 5, 2020
Prediction of response to treatment by gene expression profiling of peripheral blood in patients with microscopic
Akihiro Ishizu1, Utano Tomaru, Taichi Murai
1Faculty of Health Sciences, Hokkaido University, Sapporo, Japan. aishizu@med.hokudai.ac.jp
Abstract:
The JMAAV study was an open-labeled prospective clinical trial, which proposed severity-based treatment protocols for patients with microscopic polyangiitis (MPA). The results suggest that the proposed protocols are useful (remission rate: 89.4%), but are also indicative of relapse or patient demise regardless of the treatment (recurrence rate: 19.0%; mortality rate: 10.6%). The aim of this study is to develop the method to predict response to the treatment in patients with MPA. In the present study, transcriptome analysis was performed using peripheral blood from patients enrolled in the JMAAV study before and 1-week after the beginning of treatment. The gene expression profile before treatment was not directly related to the response to the treatment. However, when the samples from 9 patients with good response (persistent remission for 18 months) were examined, the expression of 88 genes was significantly altered by the treatment. Thirty statistically reliable genes were selected, and then the alteration of expression by the treatment was examined among 22 patients, including 17 with good response, which was defined as persistent remission for 18 months and 5 with poor response, which was defined as relapse after remission or no remission. Discrimination analysis between the alteration of expression of the 30 genes by the treatment and the response identified a combination of 16 genes as the most valuable gene set to predict the response to the treatment. This preliminary study identified IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2 as the important genes that can predict the response to the treatment in patients with MPA at an early point during the therapy.
Insights
This study identified 16 key genes that predict treatment response in microscopic polyangiitis (MPA) patients. Early gene expression changes can indicate treatment success, aiding personalized therapy for MPA.
Area of Science:
- Immunology
- Genetics
- Clinical Medicine
Background:
- Microscopic polyangiitis (MPA) is a severe autoimmune disease with significant relapse and mortality rates despite current treatment protocols.
- The JMAAV study demonstrated the utility of severity-based treatment protocols for MPA, achieving an 89.4% remission rate but highlighting persistent challenges with relapse (19.0%) and mortality (10.6%).
Purpose of the Study:
- To develop a predictive method for treatment response in patients with microscopic polyangiitis (MPA).
- To identify early biomarkers of treatment efficacy in MPA patients.
Main Methods:
- Transcriptome analysis of peripheral blood samples from MPA patients before and 1 week after treatment initiation.
- Differential gene expression analysis to identify genes altered by treatment in patients with good versus poor response.
- Development of a predictive model using gene expression alterations to discriminate between treatment responders and non-responders.
Main Results:
- Gene expression profiles before treatment did not directly correlate with treatment response.
- Treatment-induced alterations in 88 genes were observed in patients with a good response (persistent remission for 18 months).
- A panel of 16 genes, including IRF7, IFIT1, and GBP-1, was identified as a valuable predictor of MPA treatment response based on early changes in gene expression.
Conclusions:
- Early changes in the expression of a specific gene set can predict treatment response in microscopic polyangiitis (MPA) patients.
- This predictive model offers a potential tool for early therapeutic strategy adjustment in MPA management.
- The identified genes represent potential novel targets or biomarkers for improving MPA treatment outcomes.
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