EBioMedicine (Dec 2024)
Involvement of Mediterranean fever gene mutations in colchicine-responsive enterocolitis: a retrospective cohort studyResearch in context
- Hiroshi Nakase,
- Kohei Wagatsuma,
- Taku Kobayashi,
- Takayuki Matsumoto,
- Motohiro Esaki,
- Kenji Watanabe,
- Reiko Kunisaki,
- Teruyuki Takeda,
- Katsuhiro Arai,
- Takashi Ibuka,
- Dai Ishikawa,
- Yuichi Matsuno,
- Hirotake Sakuraba,
- Nobuhiro Ueno,
- Kaoru Yokoyama,
- Masayuki Saruta,
- Ryota Hokari,
- Junji Yokoyama,
- Shu Tamano,
- Masanori Nojima,
- Tadakazu Hisamatsu,
- Shusaku Yoshikawa,
- Sohachi Nanjo,
- Akira Andoh,
- Takeshi Kimura,
- Makoto Ooi,
- Ryosuke Kiyomori,
- Nobuo Aoyama,
- Fumihito Hirai,
- Atsushi Yamaushi,
- Masanao Nakamura,
- Fumikazu Koyama,
- Shuhei Hosomi,
- Kazuki Kakimoto,
- Satoshi Motoya,
- Ryosuke Sakemi,
- Hideo Suzuki,
- Tadashi Hosoya,
- Ken Takeuchi,
- Manabu Shiraki,
- Hideyuki Koide,
- Ichiro Takeuchi,
- Yosuke Furui,
- Kento Yoshida,
- Ayaka Minemura,
- Asami Matsumoto,
- Kentaro Oka
Affiliations
- Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan; Corresponding author. Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuoku, Sapporo, Hokkaido, 060-8543, Japan.
- Kohei Wagatsuma
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
- Takayuki Matsumoto
- Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Shiwa, Japan
- Motohiro Esaki
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
- Kenji Watanabe
- Department of Internal Medicine for Inflammatory Bowel Diseases, Toyama University Hospital, Toyama, Japan
- Reiko Kunisaki
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan
- Teruyuki Takeda
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan
- Katsuhiro Arai
- Center for Pediatric Inflammatory Bowel Disease, Division of Gastroenterology, National Center for Child Health and Development, Setagaya-ku, Japan
- Takashi Ibuka
- Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan
- Dai Ishikawa
- Department of Gastroenterology, Juntendo University School of Medicine, Bunkyo-ku, Japan
- Yuichi Matsuno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Hirotake Sakuraba
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
- Nobuhiro Ueno
- Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan
- Kaoru Yokoyama
- Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Japan
- Masayuki Saruta
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Minato-Ku, Japan
- Ryota Hokari
- Department of Internal Medicine, National Defense Medical College, Tokorozawa, Japan
- Junji Yokoyama
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
- Shu Tamano
- Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Japan
- Masanori Nojima
- Center for Translational Research, The Institute of Medical Science, The University of Tokyo, Japan
- Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
- Shusaku Yoshikawa
- Sohachi Nanjo
- Akira Andoh
- Takeshi Kimura
- Makoto Ooi
- Ryosuke Kiyomori
- Nobuo Aoyama
- Fumihito Hirai
- Atsushi Yamaushi
- Masanao Nakamura
- Fumikazu Koyama
- Shuhei Hosomi
- Kazuki Kakimoto
- Satoshi Motoya
- Ryosuke Sakemi
- Hideo Suzuki
- Tadashi Hosoya
- Ken Takeuchi
- Manabu Shiraki
- Hideyuki Koide
- Ichiro Takeuchi
- Yosuke Furui
- Kento Yoshida
- Ayaka Minemura
- Asami Matsumoto
- Kentaro Oka
- Journal volume & issue
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Vol. 110
p. 105454
Abstract
Summary: Background: The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations. Methods: In this retrospective cohort study, we examined MEFV mutations using gene analysis, clinical information, and colchicine responsiveness. Furthermore, we examined cytokine production in exon 2-mutated THP-1 cells (a monocytic cell line) and microbiome analysis. Findings: Of the 396 patients diagnosed with IBDU, 60.1% had MEFV mutations. Exon 2 mutations were the most common (83.7%). Among patients with available clinical information, 43.3% of patients with IBDU had typical Familial Mediterranean fever (FMF). The efficacy of colchicine in patients with IBDU carrying MEFV mutations was 84.6%. Significant differences were noted in the production of inflammatory; cytokines between THP-1 cells with and without MEFV mutations. Microbial compositions differed between patients with IBDU carrying MEFV mutations and patients with IBD and healthy controls. Interpretation: Patients with IBDU carrying MEFV mutations responded well to colchicine treatment. A notable subset of patients met the criteria for typical FMF. Alterations in intestinal microbiota may contribute to disease pathogenesis. Funding: This work was supported by the Japan Agency for Medical Research and Development (21ek0410057h0003), a grant from the Uehara Memorial Foundation, and the Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for Intractable Inflammatory Bowel Disease; Grant Number 20316729).
