Prediction of response to remission induction therapy by gene expression profiling of peripheral blood in Japanese patients with microscopic polyangiitis

Akihiro Ishizu; Utano Tomaru; Sakiko Masuda; Ken-Ei Sada; Koichi Amano; Masayoshi Harigai; Yasushi Kawaguchi; Yoshihiro Arimura; Kunihiro Yamagata; Shoichi Ozaki; Hiroaki Dobashi; Sakae Homma; Yasunori Okada; Hitoshi Sugiyama; Joichi Usui; Naotake Tsuboi; Seiichi Matsuo; Hirofumi Makino; Research Committee of the Intractable Vasculitis Syndrome and the Research Committee of the Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan

doi:10.1186/s13075-017-1328-7

Prediction of response to remission induction therapy by gene expression profiling of peripheral blood in Japanese patients with microscopic polyangiitis

Arthritis Res Ther. 2017 May 31;19(1):117. doi: 10.1186/s13075-017-1328-7.

Authors

Akihiro Ishizu¹, Utano Tomaru², Sakiko Masuda³, Ken-Ei Sada⁴, Koichi Amano⁵, Masayoshi Harigai^{6

7}, Yasushi Kawaguchi⁷, Yoshihiro Arimura⁸, Kunihiro Yamagata⁹, Shoichi Ozaki¹⁰, Hiroaki Dobashi¹¹, Sakae Homma¹², Yasunori Okada¹³, Hitoshi Sugiyama¹⁴, Joichi Usui⁹, Naotake Tsuboi¹⁵, Seiichi Matsuo¹⁵, Hirofumi Makino¹⁶; Research Committee of the Intractable Vasculitis Syndrome and the Research Committee of the Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan

Affiliations

¹ Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan. aishizu@med.hokudai.ac.jp.
² Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
³ Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, 060-0812, Japan.
⁴ Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁵ Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
⁶ Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
⁸ Nephrology and Rheumatology, First Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
⁹ Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
¹⁰ Division of Rheumatology and Allergology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
¹¹ Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
¹² Department of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.
¹³ Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
¹⁴ Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
¹⁵ Department of Nephrology, Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁶ Okayama University Hospital, Okayama, Japan.

Abstract

Background: Microscopic polyangiitis (MPA), which is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis, is one of the most frequent primary vasculitides in Japan. We earlier nominated 16 genes (IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2) as predictors of response to remission induction therapy against MPA. The aim of this study is to determine the accuracy of prediction using these 16 predictors.

Methods: Thirty-nine MPA patients were selected randomly and retrospectively from the Japanese nationwide RemIT-JAV-RPGN cohort and enrolled in this study. Remission induction therapy was conducted according to the Guidelines of Treatment for ANCA-Associated Vasculitis published by the Ministry of Health, Labour, and Welfare of Japan. Response to remission induction therapy was predicted by profiling the altered expressions of the 16 predictors between the period before and 1 week after the beginning of treatment. Remission is defined as the absence of clinical manifestations of active vasculitis (Birmingham Vasculitis Activity Score 2003: 0 or 1 point). Persistent remission for 18 months is regarded as a "good response," whereas no remission or relapse after remission is regarded as a "poor response."

Results: "Poor" and "good" responses were predicted in 7 and 32 patients, respectively. Five out of 7 patients with "poor" prediction and 1 out of 32 patients with "good" prediction experienced relapse after remission. One out of 7 patients with "poor" prediction was not conducted to remission. Accordingly, the sensitivity and specificity to predict poor response was 85.7% (6/7) and 96.9% (31/32), respectively.

Conclusions: Response to remission induction therapy can be predicted by monitoring the altered expressions of the 16 predictors in the peripheral blood at an early point of treatment in MPA patients.

Keywords: Gene profiling; Microscopic polyangiitis; Peripheral blood; Prediction of response to treatment.

MeSH terms

Adult
Aged
Asian People / genetics
Cohort Studies
Female
Gene Expression Profiling
Humans
Immunosuppressive Agents / therapeutic use
Male
Microscopic Polyangiitis / blood
Microscopic Polyangiitis / drug therapy*
Microscopic Polyangiitis / genetics*
Middle Aged
Remission Induction
Retrospective Studies
Transcriptome*
Treatment Outcome

Substances

Immunosuppressive Agents