Mucosal cytokine expression associated with deep endoscopic mucosal healing in ulcerative colitis

Kazuhiko Uchiyama; Tomohisa Takagi; Katsura Mizushima; Yasuko Hirai; Eiki Murakami; Kohei Asaeda; Mariko Kajiwara-Kubota; Saori Kashiwagi; Yuki Minagawa; Yuma Hotta; Makoto Tanaka; Ken Inoue; Kazuhiro Katada; Kazuhiro Kamada; Takeshi Ishikawa; Hideyuki Konishi; Mitsuo Kishimoto; Yuji Naito; Yoshito Itoh

doi:10.1093/ecco-jcc/jjae158

Mucosal cytokine expression associated with deep endoscopic mucosal healing in ulcerative colitis

J Crohns Colitis. 2024 Oct 16:jjae158. doi: 10.1093/ecco-jcc/jjae158. Online ahead of print.

Authors

Kazuhiko Uchiyama¹, Tomohisa Takagi^{1

2}, Katsura Mizushima³, Yasuko Hirai³, Eiki Murakami¹, Kohei Asaeda¹, Mariko Kajiwara-Kubota¹, Saori Kashiwagi¹, Yuki Minagawa¹, Yuma Hotta¹, Makoto Tanaka¹, Ken Inoue¹, Kazuhiro Katada¹, Kazuhiro Kamada¹, Takeshi Ishikawa¹, Hideyuki Konishi¹, Mitsuo Kishimoto⁴, Yuji Naito³, Yoshito Itoh¹

Affiliations

¹ Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, Japan.
² Department for Medical Innovation and Translational Medical Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, Japan.
³ Department of Human Immunology and Nutrition Science, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto, Japan.
⁴ Department of Surgical Pathology, Kyoto City Hospital, Kyoto, Japan.

PMID: 39412247
DOI: 10.1093/ecco-jcc/jjae158

Abstract

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of unknown cause for which no curative treatments have been developed. Cytokines play an important role in the pathogenesis of UC, and therapies targeting specific cytokines have been successful in treating refractory UC. The purpose of this study was to measure mucosal cytokines in UC and identify those that contribute to non-relapsing mucosal healing diagnosed by endoscopy.

Methods: This prospective, observational study included 163 patients with UC. The mucosa was evaluated by Mayo Endoscopic Subscore (MES) and linked color imaging (LCI) at the time of endoscopy, and cytokine mRNA expression in biopsy tissue taken from the same site was quantified by real-time PCR and compared with endoscopic findings. The relationship between cytokine mRNA expression and endoscopic findings was investigated.

Results: Cytokines such as IFNγ, IL-1β, IL-8, IL-17A, and IL-23 were significantly elevated in proportion to endoscopic severity of MES and LCI classification.Interestingly, we found differences in the expression of cytokines (e.g., IL-22 and IL-33) between MES and LCI classification according to disease severity. Additionally, pathway analysis based on RNA sequencing compared between LCI-A and LCI-B in the patients diagnosed as MES 0 revealed that IL-5 and IL-6 are involved in the finer differences in endoscopic mucosal redness.

Conclusions: This study is the first to report the correlation between mucosal cytokine expression and the pathogenesis of mucosal healing (MH) in UC and supports the contribution of specific cytokines as molecular markers of MH or in the pathogenesis of MH in UC.

Keywords: LCI; MES; cytokine; relapse; ulcerative colitis.

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