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Original Articles
- Characteristics of monogenic inflammatory bowel disease in very early-onset cases: a Japanese multicenter registry study
- Natsuki Ito, Takahiro Kudo, Keisuke Jimbo, Ryusuke Nambu, Fumihiko Kakuta, Tatsuki Mizuochi, Takeshi Saito, Shin-ichiro Hagiwara, Naomi Iwata, Nao Tachibana, Hideki Kumagai, Takashi Ishige, Toshifumi Yodoshi, Mikihiro Inoue, Shigeo Nishimata, Hitoshi Tajiri, Eitaro Hiejima, Mika Sasaki, Sawako Kato, Hirotaka Shimizu, Yuri Hirano, Toshiaki Shimizu, Katsuhiro Arai, Japanese Pediatric Inflammatory Bowel Disease Registry (JPIBD-R)
- Received September 1, 2025 Accepted December 22, 2025 Published online February 24, 2026
- DOI: https://doi.org/10.5217/ir.2025.00203 [Epub ahead of print]
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Abstract
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ePub - Background/Aims
Very early-onset inflammatory bowel disease (VEO-IBD), defined as IBD diagnosed before 6 years of age, is highly influenced by genetic factors. Monogenic IBD is a type of enterocolitis caused by a single pathogenic variant. However, information on Asian patients with VEO-IBD and monogenic IBD is limited. This study investigated real-world data on VEOIBD and monogenic IBD in Japan.
Methods
We evaluated patients with VEO-IBD registered in the Japanese Pediatric Inflammatory Bowel Disease Registry, a multicenter prospective registry study conducted between 2012 and 2021. We categorized patients into monogenic and non-monogenic IBD groups and compared their clinical characteristics and outcomes.
Results
Among 703 pediatric patients with IBD, 68 (9.7%) had VEO-IBD. Of these, 26 (38.2%) had ulcerative colitis, 16 (23.5%) had Crohn’s disease, 23 (33.8%) had unclassified IBD (IBD-U), and 3 (4.4%) had Behçet’s disease. Genetic testing was performed in 25 patients (36.8%), and monogenic IBD was identified in 5 of the 23 patients with IBD-U (7.4% of the VEO-IBD cohort). All 5 monogenic cases presented with an IBD-U phenotype. Monogenic IBD included A20 haploinsufficiency, interleukin-10 receptor subunit alpha deficiency, chronic granulomatous disease, Wiskott–Aldrich syndrome, and Hermansky–Pudlak syndrome. Monogenic IBD was significantly associated with IBD-U phenotype (P= 0.015) and severe infections before 1 year of age (P= 0.004).
Conclusions
Patients with VEO-IBD who present an IBD-U phenotype and have a history of severe infections during infancy should be prioritized for genetic analysis to investigate the possibility of monogenic IBD.
- 1,848 View
- 87 Download
- Fecal surrogate markers strongly correlate with endoscopic findings in pediatric onset inflammatory bowel disease: a retrospective study in Japan
- Ryoko Yoshimura, Takahiro Kudo, Masanori Toda, Kosuke Kashiwagi, Masumi Nagata, Kaori Aoki, Natsuki Ito, Kazuhide Tokita, Nobuyasu Arai, Reiko Kyodo, Masamichi Sato, Eri Miyata, Keisuke Jimbo, Yoshikazu Ohtsuka, Toshiaki Shimizu, Hiromichi Shoji
- Received January 5, 2025 Accepted April 2, 2025 Published online December 12, 2025
- DOI: https://doi.org/10.5217/ir.2025.00103 [Epub ahead of print]
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Abstract
PDFPubReaderePub
- Background/Aims
Endoscopy serves as the gold standard for assessing disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers have been under exploration as potential alternatives. This study aims to examine the diagnostic effectiveness of fecal immunochemical tests, along with levels of fecal calprotectin (FC) and fecal lactoferrin (FL), in stool samples from patients with early-onset IBD.
Methods
Children with childhood-onset IBD who visited the Department of Pediatrics and Adolescent Medicine at Juntendo University Hospital between August 2019 and July 2023 were included. FC levels, FL levels, and fecal immunochemical test results were measured using a colloidal gold agglutination assay. Fecal biomarker results and endoscopic findings were reviewed retrospectively.
Results
Sixty-five patients had ulcerative colitis (UC), 20 had Crohn’s disease (CD), and 3 had unclassified IBD. The participants, aged 3–27 years (median, 18.0 years), included 56 males and 32 females. Stool samples (n = 1,105) were analyzed, from 803 with UC, 251 with CD, and 51 with IBD. Endoscopic evaluations were conducted in 45 UC patients and 18 CD patients. A significant correlation was found between the FC and FL. These biomarkers were significantly correlated with the endoscopic activity index in both UC and CD patients.
Conclusions
FC is valuable for diagnosing endoscopic inflammation and predicting recurrence. A significant correlation was observed between FC and FL. In patients with UC and CD, both markers strongly correlated with endoscopic activity. Thus, FC and FL can serve as a reliable alternative to endoscopic evaluation in pediatric patients with childhood-onset IBD.
- 1,419 View
- 129 Download
Case Report
- Miscellaneous
- A case of autoimmune enteropathy with CTLA4 haploinsufficiency
- Haruka Miyazaki, Namiko Hoshi, Michitaka Kohashi, Eri Tokunaga, Yuna Ku, Haruka Takenaka, Makoto Ooi, Nobuyuki Yamamoto, Suguru Uemura, Noriyuki Nishimura, Kazumoto Iijima, Keisuke Jimbo, Tsubasa Okano, Akihiro Hoshino, Kohsuke Imai, Hirokazu Kanegane, Ichiro Kobayashi, Yuzo Kodama
- Intest Res 2022;20(1):144-149. Published online January 22, 2021
- DOI: https://doi.org/10.5217/ir.2020.00041
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Abstract
PDFPubReaderePub
- Autoimmune enteropathy (AIE) is a rare disease, characterized by intractable diarrhea, villous atrophy of the small intestine, and the presence of circulating anti-enterocyte autoantibodies. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and mutations in FOXP3, which is a master gene of regulatory T cells (Tregs), are major causes of AIE. Recent studies have demonstrated that mutations in other Treg-associated genes, such as CD25 and CTLA4, show an IPEX-like phenotype. We present the case of a 13-year-old girl with CTLA4 haploinsufficiency, suffering from recurrent immune thrombocytopenic purpura and intractable diarrhea. We detected an autoantibody to the AIE-related 75 kDa antigen (AIE-75), a hallmark of the IPEX syndrome, in her serum. She responded well to a medium dose of prednisolone and a controlled dose of 6-mercaptopurine (6-MP), even after the cessation of prednisolone administration. Serum levels of the soluble interleukin-2 receptor and immunoglobulin G (IgG) were useful in monitoring disease activity during 6-MP therapy. In conclusion, autoimmune-mediated mechanisms, similar to the IPEX syndrome, may be involved in the development of enteropathy in CTLA4 haploinsufficiency. Treatment with 6-MP and monitoring of disease activity using serum levels of soluble interleukin-2 receptor and IgG is suggested for such cases.
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Citations
Citations to this article as recorded by
- Diagnostic clues in patients with clinical malabsorption and pathological small intestinal villous atrophy: Immune-mediated type and beyond
Mu-Han Li, Qi-Pu Wang, Cheng-Zhu Ou, Tian-Ming Xu, Yang Chen, Hao Tang, Yan Zhang, Yan-Jun Lai, Xu-Zhen Qin, Ji Li, Wei-Xun Zhou, Jing-Nan Li
World Journal of Gastroenterology.2026;[Epub] CrossRef - Clinical and genetic features of CTLA-4 haploinsufficiency: a prospective study in China
Guishan Liu, Jingyuan Zhang, Di Wu, Jin Xu, Jiayuan Dai, Min Shen
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Grigorios Christodoulidis, Sara E Agko, Marina N Kouliou, Konstantinos E Koumarelas, Dimitris Zacharoulis
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Manuel A. Baarslag, Joosje H. Heimovaara, Jessica S.W. Borgers, Koen J. van Aerde, Hans J.P.M. Koenen, Ruben L. Smeets, Pauline L.M. Buitelaar, Dick Pluim, Shoko Vos, Stefanie S.V. Henriet, Jan Willem B. de Groot, Martine van Grotel, Hilde Rosing, Jos H.
New England Journal of Medicine.2023; 389(19): 1790. CrossRef - Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study
Akihiro Hoshino, Etsushi Toyofuku, Noriko Mitsuiki, Motoi Yamashita, Keisuke Okamoto, Michio Yamamoto, Kenji Kanda, Genki Yamato, Dai Keino, Yuri Yoshimoto-Suzuki, Junji Kamizono, Yasuhiro Onoe, Takuya Ichimura, Mika Nagao, Masaru Yoshimura, Koji Tsugawa,
Frontiers in Immunology.2022;[Epub] CrossRef - Treg specialization and functions beyond immune suppression
Jillian L Astarita, Claudia X Dominguez, Corey Tan, Jovanny Guillen, Mariela L Pauli, Rosario Labastida, Jose Valle, Melanie Kleinschek, Jesse Lyons, Ali A Zarrin
Clinical and Experimental Immunology.2022;[Epub] CrossRef
- Diagnostic clues in patients with clinical malabsorption and pathological small intestinal villous atrophy: Immune-mediated type and beyond
- 12,577 View
- 439 Download
- 11 Web of Science
- 10 Crossref
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