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- 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
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ePub - 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
BMC Rheumatology.2026;[Epub] CrossRef - Pathological perspectives on immune-related adverse events
Terufumi Kubo, Rena Morita, Kenta Sasaki, Naoki Shijubou, Kenji Murata, Tomohide Tsukahara, Toshihiko Torigoe, Yoshihiko Hirohashi
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Grigorios Christodoulidis, Sara E Agko, Marina N Kouliou, Konstantinos E Koumarelas, Dimitris Zacharoulis
World Journal of Gastroenterology.2025;[Epub] CrossRef - Non-Celiac Villous Atrophy—A Problem Still Underestimated
Katarzyna Napiórkowska-Baran, Paweł Treichel, Adam Wawrzeńczyk, Ewa Alska, Robert Zacniewski, Maciej Szota, Justyna Przybyszewska, Amanda Zoń, Zbigniew Bartuzi
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Laila M. Rad, Gabriel Arellano, Joseph R. Podojil, Jessica J. O’Konek, Lonnie D. Shea, Stephen D. Miller
Journal of Allergy and Clinical Immunology.2024; 153(3): 549. CrossRef - Understanding the Spectrum of Immune Dysregulation Manifestations in Autoimmune Lymphoproliferative Syndrome and Autoimmune Lymphoproliferative Syndrome-like Disorders
Christopher Failing, Jennifer R. Blase, Kelly Walkovich
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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
- 12,578 View
- 439 Download
- 11 Web of Science
- 10 Crossref
Original Article
- Inflammatory Bowel Diseases
- Prospective validation of CD4+CD25+FOXP3+ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn’s disease
- Ritika Rampal, Saurabh Kedia, Mohamad Nahidul Wari, Deepak Madhu, Amit Kumar Singh, Veena Tiwari, V. Pratap Mouli, Srikant Mohta, Govind Makharia, Vineet Ahuja
- Intest Res 2021;19(2):232-238. Published online May 8, 2020
- DOI: https://doi.org/10.5217/ir.2019.09181
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Abstract
PDFPubReaderePub
- Background/Aims
Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4+CD25+FOXP3+ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients.
Methods
Seventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients.
Results
Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33–50] vs. 24.9 [interquartile range, 14.4–29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65–0.89) and a FOXP3+ cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n = 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68–0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD.
Conclusions
The current findings validate that the increased frequency of CD4+CD25+FOXP3+ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD. -
Citations
Citations to this article as recorded by- The Overlap Between Crohn’s Disease and Intestinal Tuberculosis: A Never-Ending Story
Sergiu Marian Cazacu, Costin Teodor Streba, Cristian Constantin, Claudiu Marinel Ionele, Ion Rogoveanu, Alexandru Valentin Popescu, Mirela-Marinela Florescu
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Chuyao Zhang, Xiaoyin Zhang
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Susama Patra, Shalini Chaudhary, Subash Chandra Samal, Pavithra Ayyanar, Somanath Padhi, Hemanta Kumar Nayak, Amit Kumar Satapathy, Saurav Nayak, Ajit Sahu, Tapaskanti Parida, Mohammed Shahin
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Himanshu Narang, Saurabh Kedia, Vineet Ahuja
Current Opinion in Infectious Diseases.2024; 37(5): 392. CrossRef - Evidence-based approach to diagnosis and management of abdominal tuberculosis
Daya Krishna Jha, Mythili Menon Pathiyil, Vishal Sharma
Indian Journal of Gastroenterology.2023; 42(1): 17. CrossRef - Gut Microbiome in Probable Intestinal Tuberculosis and Changes following Anti-Tuberculosis Treatment
Hyuk Yoon, Young Soo Park, Cheol Min Shin, Nayoung Kim, Dong Ho Lee
Yonsei Medical Journal.2022; 63(1): 34. CrossRef - Single-nucleotide polymorphisms and activities of indoleamine 2,3-dioxygenase isoforms, IDO1 and IDO2, in tuberculosis patients
Tingming Cao, Guangming Dai, Hongqian Chu, Chengcheng Kong, Huijuan Duan, Na Tian, Zhaogang Sun
Hereditas.2022;[Epub] CrossRef - Recent advances in the diagnosis of intestinal tuberculosis
Hasan Maulahela, Marcellus Simadibrata, Erni Juwita Nelwan, Nur Rahadiani, Editha Renesteen, S. W. T. Suwarti, Yunita Windi Anggraini
BMC Gastroenterology.2022;[Epub] CrossRef - Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis
Saurabh Kedia, Raju Sharma, Sudheer Kumar Vuyyuru, Deepak Madhu, Pabitra Sahu, Bhaskar Kante, Prasenjit Das, Ankur Goyal, Karan Madan, Govind Makharia, Vineet Ahuja
Intestinal Research.2022; 20(2): 184. CrossRef - Inflammatory bowel disease in Korea: epidemiology and pathophysiology
Jung Won Lee, Chang Soo Eun
The Korean Journal of Internal Medicine.2022; 37(5): 885. CrossRef - Intestinal tuberculosis or Crohn's disease: Illusion or delusion or allusion
Saurabh Kedia, Vineet Ahuja
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Jung Min Kim, Jun Gu Kang, Sungwon Kim, Jae Hee Cheon
Journal of Gastroenterology and Hepatology.2021; 36(8): 2141. CrossRef - Mycobacterium tuberculosis (MTB) antigen-induced upregulation of interleukin-35 expression in patients with MTB infection: In vitro blockade of the effects of interleukin-35 on T lymphocyte subsets
Hongbin Jiang, Beinian Cui, Jun Zhang
Pathogens and Disease.2021;[Epub] CrossRef
- The Overlap Between Crohn’s Disease and Intestinal Tuberculosis: A Never-Ending Story
- 9,050 View
- 156 Download
- 10 Web of Science
- 13 Crossref
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