Journal of Gastroenterology最新文献

{"title":"Conditional deletion of IP₃R1 by Islet1-Cre in mice reveals a critical role of IP₃R1 in interstitial cells of Cajal in regulating GI motility.","authors":"Hong Wang, Beili Zhao, Lei Huang, Xiangbin Zhu, Na Li, Can Huang, Zhen Han, Kunfu Ouyang","doi":"10.1007/s00535-024-02164-1","DOIUrl":"10.1007/s00535-024-02164-1","url":null,"abstract":"<p><strong>Background and aims: </strong>Inositol 1,4,5-trisphosphate receptor type 1 (IP₃R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP₃R1 deletion strategies to address this question in mice.</p><p><strong>Methods: </strong>Conditional IP₃R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-Cre^EGFP were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro.</p><p><strong>Results: </strong>In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP₃R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP₃R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-Cre^EGFP only targeted SMCs in the mouse GI tract. Although IP₃R1 deletion by smMHC-Cre^EGFP (smR1KO) also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice.</p><p><strong>Conclusions: </strong>IP₃R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP₃R1 in ICCs plays an essential role in regulating GI motility in vivo.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"152-165"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of ursodeoxycholic acid treatment on Fontan-associated liver disease.","authors":"Tomomi Kogiso, Yuri Ogasawara, Makiko Taniai, Eriko Shimada, Kei Inai, Katsutoshi Tokushige, Yousuke Nakai","doi":"10.1007/s00535-024-02168-x","DOIUrl":"10.1007/s00535-024-02168-x","url":null,"abstract":"<p><strong>Background: </strong>Fontan-associated liver disease (FALD) is a type of progressive liver fibrosis that occurs following Fontan surgery and can be complicated by hepatocellular carcinoma (HCC). Established treatments for FALD are lacking. Therefore, we investigated the efficacy of ursodeoxycholic acid (UDCA) in patients with FALD.</p><p><strong>Methods: </strong>This single-center retrospective study was conducted from 2003 to 2024 and involved 220 patients (103 men, 46.8%) who had been diagnosed with FALD. UDCA was administered to 113 patients presenting with liver or biliary enzyme abnormalities. We evaluated the patients' liver enzyme levels 3, 6, and 12 months after treatment. HCC developed in 10.5% and the mortality rate was 4.5%. Survival and cumulative incidence of HCC were compared between patients with and without UDCA treatment using Kaplan-Meier curves and propensity-matched analysis (n = 68 per group).</p><p><strong>Results: </strong>UDCA treatment significantly reduced the aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transferase (GGT) levels at 3 months. The mean pretreatment AST/ALT/GGT levels were 26/22/323 U/L, respectively, and decreased to 19/15/102 U/L at 3 months, 18/12/88 U/L at 6 months, and 16/19/64 U/L at 12 months. However, the total bilirubin level and platelet count did not show significant differences. The survival rate was higher and the HCC rate was lower in patients with than without UDCA treatment. The 5-year incidence rate of HCC was 5.6% in the UDCA group and 24.2% in the untreated group.</p><p><strong>Conclusions: </strong>UDCA treatment significantly reduced liver enzyme levels, including GGT, and mitigated the progression of HCC. UDCA may be beneficial for patients with FALD.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"210-221"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142729600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of long-term trends on outcomes in the management of colonic diverticular bleeding: mediation analyses in a large multicenter study.","authors":"Kazuyuki Narimatsu, Naoki Ishii, Atsuo Yamada, Tomonori Aoki, Katsumasa Kobayashi, Atsushi Yamauchi, Jun Omori, Takashi Ikeya, Taiki Aoyama, Naoyuki Tominaga, Yoshinori Sato, Takaaki Kishino, Tsunaki Sawada, Masaki Murata, Akinari Takao, Kazuhiro Mizukami, Ken Kinjo, Shunji Fujimori, Takahiro Uotani, Minoru Fujita, Hiroki Sato, Sho Suzuki, Toshiaki Narasaka, Junnosuke Hayasaka, Tomohiro Funabiki, Yuzuru Kinjo, Akira Mizuki, Shu Kiyotoki, Tatsuya Mikami, Ryosuke Gushima, Hiroyuki Fujii, Yuta Fuyuno, Takuto Hikichi, Yosuke Toya, Noriaki Manabe, Koji Nagaike, Tetsu Kinjo, Yorinobu Sumida, Sadahiro Funakoshi, Kiyonori Kobayashi, Tamotsu Matsuhashi, Yuga Komaki, Ryota Hokari, Mitsuru Kaise, Naoyoshi Nagata","doi":"10.1007/s00535-024-02178-9","DOIUrl":"10.1007/s00535-024-02178-9","url":null,"abstract":"<p><strong>Background: </strong>Despite accumulating evidence and recommendations for management of colonic diverticular bleeding (CDB), the changes in its clinical management and outcomes remain unknown.</p><p><strong>Methods: </strong>We performed a retrospective tendency analysis on a biennial basis, a propensity score-matched cohort study between the first and latter half groups, and mediation analyses to compare the diagnostic and treatment methods between January 2010 and December 2019 (CODE BLUE-J Study).</p><p><strong>Results: </strong>A total of 6575 patients with CDB were included. While the use of colonoscopy as the initial diagnostic procedure declined, the use of computed tomography (CT) increased in both the trend test and before-and-after comparisons. In hemostasis therapy, the use of endoscopic clips declined and band ligation increased. Interventional radiology remained unchanged; however, the number of surgeries decreased over time. The stigmata of recent hemorrhage (SRH) detection rate and length of hospital stay (LOS) improved significantly. Mediation analyses showed that use of a distal attachment and water-jet scope contributed to an improved SRH detection rate, and use of band ligation contributed to preventing rebleeding within 30 days.</p><p><strong>Conclusions: </strong>Management strategies for CDB have changed in the past decade, particularly regarding the increased use of CT and decreased need for surgery. However, the main outcomes, except for the SRH detection rate and LOS, did not improve. The widespread use of distal attachment, water-jet scope, and band ligation could improve outcomes in CDB management.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"174-186"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher Correction: Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study.","authors":"Makoto Okabe, Shuji Yamamoto, Masahiro Shiokawa, Tadakazu Hisamatsu, Hajime Yamazaki, Risa Nakanishi, Kensuke Hamada, Hiroki Kitamoto, Takeshi Kuwada, Norimitsu Uza, Aki Sakatani, Toshimitsu Fujii, Masashi Ohno, Minoru Matsuura, Tomoyoshi Shibuya, Naoki Ohmiya, Makoto Ooi, Namiko Hoshi, Kei Moriya, Kiichiro Tsuchiya, Yoshiharu Yamaguchi, Reiko Kunisaki, Masahiro Takahara, Tomohisa Takagi, Tetsuo Takehara, Fumihito Hirai, Kazuki Kakimoto, Motohiro Esaki, Hiroshi Nakase, Fukunori Kinjo, Takehiro Torisu, Shuji Kanmura, Kazuyuki Narimatsu, Katsuyoshi Matsuoka, Hiroto Hiraga, Kaoru Yokoyama, Yusuke Honzawa, Makoto Naganuma, Masayuki Saruta, Yuzo Kodama, Tsutomu Chiba, Hiroshi Seno","doi":"10.1007/s00535-024-02203-x","DOIUrl":"10.1007/s00535-024-02203-x","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"263-264"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to \"Severe ulcerative colitis: diagnostic criteria and therapy\".","authors":"Makoto Naganuma","doi":"10.1007/s00535-024-02200-0","DOIUrl":"10.1007/s00535-024-02200-0","url":null,"abstract":"","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"259"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of optimal cutoff value of ulcerative colitis intestinal ultrasound index to estimate endoscopic improvement in ulcerative colitis.","authors":"Haruka Komatsu, Hiromu Morikubo, Yoko Kimura, Chihiro Moue, Hiromi Yonezawa, Minoru Matsuura, Jun Miyoshi, Tadakazu Hisamatsu","doi":"10.1007/s00535-024-02172-1","DOIUrl":"10.1007/s00535-024-02172-1","url":null,"abstract":"<p><strong>Background: </strong>The ulcerative colitis intestinal ultrasound (UC-IUS) index (UII) has been reported as a sonographic scoring system correlating with the Mayo endoscopic subscore (MES). Endoscopic improvement (EI) of UC (MES ≤ 1) is a crucial therapeutic target in clinical practice. However, the cutoff value for estimating EI using the UII has not been established.</p><p><strong>Methods: </strong>We established test and validation cohorts comprising patients with UC undergoing IUS and endoscopy within a 15-day interval at our institution. IUS findings (bowel wall thickness, bowel blood flow, bowel wall structure, haustrations, and inflammatory fat) and endoscopic activity (MES) of each colon segment (ascending, transverse, descending, and sigmoid colon) were assessed.</p><p><strong>Results: </strong>In the test cohort (74 segments), UII was correlated with MES (r = 0.645, p < 0.0001). The median UII was 1.0 and 6.0 among participants with MES ≤ 1 and MES ≥ 2, respectively. A UII of 2 was identified as the threshold for estimating MES ≤ 1 with receiver operating characteristic analysis. In the validation cohort (122 segments), UII was correlated with MES (r = 0.675, p < 0.0001) and the estimation ability of UII ≤ 2 for EI had a positive predictive value of 85.4% and negative predictive value of 79.0%. This estimation ability of UII for EI was numerically lower but not statistically different from the previously reported Milan Ultrasound Criteria and Kyorin Ultrasound Criterion for UC.</p><p><strong>Conclusion: </strong>UII ≤ 2 can be a simple, feasible criterion for estimating EI. Correlation with MES is an advantage of the UII compared with other criteria. Proper use of various sonographic criteria is important.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"166-173"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis.","authors":"Chunmei Wen, Huihui Tao, Huaizhou Chen, Wenjun Pu, Qiang Yan, Yaoshuang Zou, Sheng Sean Su, Lingling Zhou, Yali Peng, Guoying Wang, Tiantian Xu, Xuejia Zheng, Mengyao Wu, Yong Dai","doi":"10.1007/s00535-025-02218-y","DOIUrl":"https://doi.org/10.1007/s00535-025-02218-y","url":null,"abstract":"<p><strong>Background: </strong>Liver cirrhosis represents a critical stage of chronic liver disease, characterized by progressive liver damage, cellular dysfunction, and disrupted cell-to-cell interactions. Glycosylation, an essential post-translational modification, significantly influences cellular behavior and disease progression. Its role in cirrhosis at the single-cell level remains unclear, despite its importance.</p><p><strong>Methods: </strong>This study, based on single-cell glycosylation and transcriptome data, compared the expression of differentially expressed genes in liver tissues from cirrhotic and healthy control samples, identifying changes in glycosylation-related genes and their functional pathway enrichment characteristics. Additionally, it analyzed the composition of immune cells and intercellular interaction features, with a focus on the interaction between macrophages and other immune cells and their potential role in immune regulation.</p><p><strong>Results: </strong>The analysis revealed significant changes in immune cell composition and glycosylation patterns in cirrhotic livers. Specifically, the number of macrophages increased substantially, while overall glycosylation levels decreased. Enhanced interactions between macrophages and other cell types were observed, highlighting the central role of macrophages in reshaping the immune microenvironment during cirrhosis progression. Gene expression analysis showed a marked upregulation of FUCA1, a gene encoding a glycosylation-related hydrolase. This change was strongly associated with the observed reduction in glycosylation levels. Functional enrichment analysis further revealed that glycosylation-related genes were primarily involved in immune pathways, including antigen processing and presentation, cytokine signaling, and immune activation.</p><p><strong>Conclusions: </strong>Single-cell glycosylation analysis provides crucial insights into immune cell interactions in cirrhosis. Targeting glycosylation pathways in macrophages may offer new treatment strategies for cirrhosis.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis- and stemness inhibition-mediated therapeutic potency of ferrous oxide nanoparticles-diethyldithiocarbamate using a co-spheroid 3D model of pancreatic cancer.","authors":"Marwa M Abu-Serie, Ana K Gutiérrez-García, Macie Enman, Utpreksha Vaish, Huma Fatima, Vikas Dudeja","doi":"10.1007/s00535-025-02213-3","DOIUrl":"https://doi.org/10.1007/s00535-025-02213-3","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and exhibits a limited response to apoptosis-dependent chemotherapeutic drugs (e.g., gemcitabine, Gem). This is mainly attributed to the antioxidant defense system (glutathione and aldehyde dehydrogenase (ALDH) 1A1), which sustains stemness features of cancer stem cells (CSCs) and activated pancreatic stellate cells (PSCs)-generated excess stromal proteins. This dense stroma retards drug delivery.</p><p><strong>Methods: </strong>This study established co-spheroid model consisting of mouse PDAC cell line (KPC) and PSCs (1:5) to accurately investigate the anti-PDAC activity of nanocomplex of ferrous oxide nanoparticles-diethyldithiocarbamate (FeO NPs-DE), compared to Gem, using in vitro and in vivo 3D models.</p><p><strong>Results: </strong>In vitro and in vivo co-spheroid models demonstrated higher therapeutic efficacy of FeO NPs-DE than Gem. FeO NPs-DE induced selective accumulation of iron-dependent ferroptosis (non-apoptosis)-generated a lethal lipid peroxidation that was potentiated by DE-mediated glutathione and ALDH1A1 suppression. This led to collapse of stemness, as evidenced by down-regulating CSC genes and p-AKT protein expression. Subsequently, gene and/or protein levels of PSC activators (transforming growth factor (TGF)-β, plasminogen activator inhibitor-1, ZEB1, and phosphorylated extracellular signal-regulated kinase) and stromal proteins (collagen 1A2, smooth muscle actin, fibronectin, and matrix metalloproteinase-9) were suppressed. Moreover, DE of nanocomplex enhanced caspase 3-dependent apoptosis with diminishing the main oncogene, BCL-2.</p><p><strong>Conclusions: </strong>FeO NPs-DE had a stronger eradicating effect than Gem on primary and metastatic peritoneal PDAC tumors. This nanocomplex-mediated ferroptosis and stemness inhibition provides an effective therapeutic approach for PDAC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.","authors":"Xiaoli Zhang, Jianzhou Li, Yichen Yao, Mimi Zhou, Yingli He, Yalei Zhao","doi":"10.1007/s00535-025-02212-4","DOIUrl":"https://doi.org/10.1007/s00535-025-02212-4","url":null,"abstract":"<p><strong>Background: </strong>We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes.</p><p><strong>Results: </strong>Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4^high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions.</p><p><strong>Conclusions: </strong>TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-integrin αvβ6 autoantibody in primary sclerosing cholangitis: a Japanese nationwide study.","authors":"Muneji Yasuda, Masahiro Shiokawa, Takeshi Kuwada, Yoshihiro Nishikawa, Risa Nakanishi, Ikuhisa Takimoto, Koki Chikugo, Masataka Yokode, Yuya Muramoto, Shimpei Matsumoto, Takeharu Nakamura, Sakiko Ota, Tomoaki Matsumori, Keiko Kuroda, Takahisa Hachiya, Hajime Yamazaki, Norimitsu Uza, Yuzo Kodama, Tsutomu Chiba, Toshio Fujisawa, Atsumasa Komori, Masanori Abe, Izumi Yamaguchi, Fumihiko Matsuda, Hiroyuki Isayama, Atsushi Tanaka, Hiroshi Seno","doi":"10.1007/s00535-024-02169-w","DOIUrl":"10.1007/s00535-024-02169-w","url":null,"abstract":"<p><strong>Background: </strong>Although specific biomarkers for primary sclerosing cholangitis (PSC) are required, no such biomarkers have been identified. We previously reported that patients with PSC had anti-integrin αvβ6 autoantibodies at only two hospitals. In this study, we aimed to validate the accuracy of the autoantibodies in diagnosing PSC using the newly developed Anti-integrin αvβ6 enzyme-linked immunosorbent assay (ELISA) Kit, which enables quantitation and comparison of antibodies among different facilities.</p><p><strong>Methods: </strong>Overall, 81 patients with PSC in a Japanese PSC registry recruited from 17 medical centers and hospitals, and 358 controls were enrolled. We retrospectively assessed anti-integrin αvβ6 autoantibodies using the Anti-integrin αvβ6 ELISA Kit and in-house ELISA.</p><p><strong>Results: </strong>Anti-Integrin αvβ6 ELISA Kit and in-house ELISA exhibited a significant correlation (r = 0.97, P < 0.001). Anti-integrin αvβ6 autoantibodies were detected in 67 of 81 (82.7%) patients with PSC and 20 of 358 (5.6%) controls, resulting in a sensitivity of 82.7% and specificity of 94.4% for PSC, using the anti-integrin αvβ6 ELISA Kit. When focusing on the presence or absence of inflammatory bowel disease (IBD), the sensitivities for PSC with ulcerative colitis, Crohn's disease, unclassified-IBD, and without IBD were 97.8% (43/44), 100% (1/1), 80.0% (8/10), and 53.8% (7/13), respectively. Antibody concentrations were significantly higher in PSC patients without IBD than in controls (P < 0.001).</p><p><strong>Conclusions: </strong>We validated that anti-integrin αvβ6 autoantibodies have high sensitivity and specificity for diagnosing PSC. This study provides further evidence that anti-integrin αvβ6 autoantibodies are a useful biomarker for diagnosing PSC.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":"118-126"},"PeriodicalIF":6.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11717786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}