title: Prediction of response to treatment by gene expression profiling of peripheral blood in patients with microscopic polyangiitis.
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.
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo, Japan. aishizu@med.hokudai.ac.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.forename: Taichi
authors.initials: T
authors.lastname: Murai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshiki
authors.forename: Wako
authors.initials: W
authors.lastname: Yumura
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Yamada
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
authors.forename: Manae S
authors.initials: MS
authors.lastname: Kurokawa
authors.forename: Machi
authors.initials: M
authors.lastname: Suka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ozaki
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D015331:Cohort Studies; D016002:Discriminant Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D055953:Microscopic Polyangiitis / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests
chemical_list: D000305:Adrenal Cortex Hormones; D005819:Genetic Markers; D007166:Immunosuppressive Agents