Multicenter Study

. 2025 Jan;60(1):86-95.

doi: 10.1007/s00535-024-02176-x. Epub 2024 Nov 28.

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

Makoto Okabe¹, Shuji Yamamoto^#², Masahiro Shiokawa^#³, Tadakazu Hisamatsu^#⁴, Hajime Yamazaki⁵, Risa Nakanishi¹, Kensuke Hamada¹, Hiroki Kitamoto¹, Takeshi Kuwada¹, Norimitsu Uza¹, Aki Sakatani⁶, Toshimitsu Fujii⁷, Masashi Ohno⁸, Minoru Matsuura⁹, Tomoyoshi Shibuya¹⁰, Naoki Ohmiya¹¹, Makoto Ooi¹², Namiko Hoshi¹², Kei Moriya¹³, Kiichiro Tsuchiya¹⁴, Yoshiharu Yamaguchi¹⁵, Reiko Kunisaki¹⁶, Masahiro Takahara¹⁷, Tomohisa Takagi¹⁸, Tetsuo Takehara¹⁹, Fumihito Hirai²⁰, Kazuki Kakimoto²¹, Motohiro Esaki²², Hiroshi Nakase²³, Fukunori Kinjo²⁴, Takehiro Torisu²⁵, Shuji Kanmura²⁶, Kazuyuki Narimatsu²⁷, Katsuyoshi Matsuoka²⁸, Hiroto Hiraga²⁹, Kaoru Yokoyama³⁰, Yusuke Honzawa³¹, Makoto Naganuma³¹, Masayuki Saruta³², Yuzo Kodama¹², Tsutomu Chiba³³, Hiroshi Seno¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
² Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. shuyama@kuhp.kyoto-u.ac.jp.
³ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. machan@kuhp.kyoto-u.ac.jp.
⁴ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan. thisamatsu@ks.kyorin-u.ac.jp.
⁵ Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
⁶ Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, 078-8510, Japan.
⁷ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
⁸ Department of Medicine, Shiga University of Medical Science, Otsu, 520-2192, Japan.
⁹ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan.
¹⁰ Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
¹¹ Department of Advanced Endoscopy, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan.
¹² Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.
¹³ Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, 630-8581, Japan.
¹⁴ Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, 305-8576, Japan.
¹⁵ Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
¹⁶ Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, 232-0024, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, 700-8558, Japan.
¹⁸ Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
²⁰ Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
²¹ Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, 569-8686, Japan.
²² Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan.
²³ Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
²⁴ Center for Gastroenterology, Urasoe General Hospital, Urasoe, 901-2102, Japan.
²⁵ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
²⁶ Division of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan.
²⁷ Department of Internal Medicine, National Defence Medical College, Tokorozawa, 359-8513, Japan.
²⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, 285-8741, Japan.
²⁹ Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8563, Japan.
³⁰ Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, 252-0375, Japan.
³¹ Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Osaka, 573-1010, Japan.
³² Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, 105-8471, Japan.
³³ Department of Gastroenterology and Hepatology, Kansai Electric Power Hospital, Fukushima-ku, Osaka, 553-0003, Japan.

^# Contributed equally.

PMID: 39607498
PMCID: PMC11717824
DOI: 10.1007/s00535-024-02176-x

Multicenter Study

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

Makoto Okabe et al. J Gastroenterol. 2025 Jan.

. 2025 Jan;60(1):86-95.

doi: 10.1007/s00535-024-02176-x. Epub 2024 Nov 28.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
² Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. shuyama@kuhp.kyoto-u.ac.jp.
³ Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. machan@kuhp.kyoto-u.ac.jp.
⁴ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan. thisamatsu@ks.kyorin-u.ac.jp.
⁵ Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
⁶ Division of Gastroenterology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, 078-8510, Japan.
⁷ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-8519, Japan.
⁸ Department of Medicine, Shiga University of Medical Science, Otsu, 520-2192, Japan.
⁹ Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, 181-8611, Japan.
¹⁰ Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, 113-8421, Japan.
¹¹ Department of Advanced Endoscopy, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan.
¹² Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan.
¹³ Department of Gastroenterology, Nara Prefecture General Medical Center, Nara, 630-8581, Japan.
¹⁴ Department of Gastroenterology, Institute of Medicine, University of Tsukuba, Tsukuba, 305-8576, Japan.
¹⁵ Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, 480-1195, Japan.
¹⁶ Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, 232-0024, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, 700-8558, Japan.
¹⁸ Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
¹⁹ Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
²⁰ Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, 814-0180, Japan.
²¹ Second Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, 569-8686, Japan.
²² Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan.
²³ Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, 060-8543, Japan.
²⁴ Center for Gastroenterology, Urasoe General Hospital, Urasoe, 901-2102, Japan.
²⁵ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
²⁶ Division of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8520, Japan.
²⁷ Department of Internal Medicine, National Defence Medical College, Tokorozawa, 359-8513, Japan.
²⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, 285-8741, Japan.
²⁹ Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, 036-8563, Japan.
³⁰ Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, 252-0375, Japan.
³¹ Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kansai Medical University, Osaka, 573-1010, Japan.
³² Division of Internal Medicine, Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, 105-8471, Japan.
³³ Department of Gastroenterology and Hepatology, Kansai Electric Power Hospital, Fukushima-ku, Osaka, 553-0003, Japan.

^# Contributed equally.

PMID: 39607498
PMCID: PMC11717824
DOI: 10.1007/s00535-024-02176-x

Erratum in

Publisher Correction: Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study.
Okabe M, Yamamoto S, Shiokawa M, Hisamatsu T, Yamazaki H, Nakanishi R, Hamada K, Kitamoto H, Kuwada T, Uza N, Sakatani A, Fujii T, Ohno M, Matsuura M, Shibuya T, Ohmiya N, Ooi M, Hoshi N, Moriya K, Tsuchiya K, Yamaguchi Y, Kunisaki R, Takahara M, Takagi T, Takehara T, Hirai F, Kakimoto K, Esaki M, Nakase H, Kinjo F, Torisu T, Kanmura S, Narimatsu K, Matsuoka K, Hiraga H, Yokoyama K, Honzawa Y, Naganuma M, Saruta M, Kodama Y, Chiba T, Seno H. Okabe M, et al. J Gastroenterol. 2025 Feb;60(2):263-264. doi: 10.1007/s00535-024-02203-x. J Gastroenterol. 2025. PMID: 39729094 Free PMC article. No abstract available.

Abstract

Background: A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study.

Methods: We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn's disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities.

Results: We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers.

Conclusions: The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study.

Keywords: Anti-integrin αvβ6 antibody; Colonic Crohn’s disease; Diagnostic biomarker; Ulcerative colitis.

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Conflict of interest statement

Declarations. Conflict of interest: Masahiro Shiokawa received patent royalties and research grants from Medical and Biological Laboratories Co., Ltd. Tadakazu Hisamatsu received consulting fees from Mitsubishi Tanabe Pharma Co., EA Pharma Co., Abbvie GK., Janssen Pharmaceutical K.K, Nichi-Iko Pharmaceutical Co., Ltd., Eli Lilly, and Gilead Sciences Inc., honorariums from Mitsubishi Tanabe Pharma Co., Abbvie GK., EA Pharma Co., Kyorin Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Janssen Pharmaceutical K.K, Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., and Kissei Pharmaceutical Co., Ltd., and research grants from EA Pharma Co., Abbvie GK., Pfizer Inc., Mitsubishi Tanabe Pharma Co., Kyorin Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Nippon Kayaku Co. Ltd., and Boston Scientific Corporation. Hajime Yamazaki received research grants from Takeda Pharmaceutical Co., Ltd. Aki Sakatani received endowed chair from Toukeikai Kyoritsu Hospital. Toshimitsu Fujii received honorariums from Abbvie GK., Janssen Pharmaceutical K.K, Mitsubishi Tanabe Pharma Co. and Takeda Pharmaceutical Co., Ltd., and research grants from Abbvie GK., Alfresa Pharma Co., Boehringer Ingelheim co., Bristol-Myers Squibb, Celgene Inc., Celltrion Inc., EA Pharma Co., Eli Lilly Japan K.K., Gilead Sciences Inc., Janssen Pharmaceutical KK., Kissei Pharmaceutical Co., Ltd., Mebix Inc., Sanofi Ltd., and Takeda Pharmaceutical Co., Ltd. Minoru Matsuura received honorariums from Janssen Pharmaceutical K.K., and Abbvie GK. Reiko Kunisaki received honorariums from Abbvie GK., Janssen Pharmaceutical K.K, Mitsubishi Tanabe Pharma Co., and Takeda Pharmaceutical Co., Ltd., and research grants from Eli Lilly Japan K.K., Janssen Pharmaceutical K.K, and Takeda Pharmaceutical Co., Ltd. Tomohisa Takagi received honorariums from Janssen Pharmaceutical K.K, Mitsubishi Tanabe Pharma Co., Towa Pharmaceutical Co., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Abbvie GK., EA Pharma Co., Ltd., and Pfizer Japan Inc., research grants from PreMedia Inc., and scholarship grants from Mitsubishi Tanabe Pharma Co. Tetsuo Takehara received honorariums from Abbvie GK., Gilead Sciences Inc., research grants from Gilead Sciences Inc., Janssen Pharmaceutical K.K, and scholarship grants from Abbvie GK., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., and Nippon Kayaku Co., Ltd. Fumihito Hirai received honorariums from Abbvie GK., EA Pharma Co., Ltd., Janssen Pharmaceutical K.K, Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Takeda Pharmaceutical Co., Ltd., research grants from Eli Lilly Japan K.K., Janssen Pharmaceutical K.K, and Abbvie GK., and scholarship grants from Abbvie GK., EA Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Mitsubishi Tanabe Pharma Co. Motohiro Esaki received honorariums from Abbvie GK., Mitsubishi Chemical Group Co., EA Pharma Co., Ltd., Janssen Pharmaceutical K.K, Takeda Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Hiroshi Nakase received honorariums from Abbvie GK., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Janssen Pharmaceutical K.K, Gilead Sciences Inc., Pfizer Inc., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., VIATRIS Inc, and JIMRO Co., Ltd., research grants from Abbvie GK. and Hoya group Pentax Medical, scholarship grants from Nippon Kayaku Co., Mochida Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Zeria Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co. and EA Pharma Co., Ltd., and endowed chair from Miyarisan Pharmaceutical Co., Ltd., JIMRO Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Kyorin Pharmaceutical Co., Ltd. Katsuyoshi Matsuoka received honorariums from Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Abbvie GK, EA Pharma Co., Ltd., Pfizer Inc., Mochida Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Gilead Sciences, and Eli Lilly Japan K.K., research grants from Janssen Pharmaceutical K.K., and scholarship grants from Mochida Pharmaceutical Co., Ltd. and EA Pharma Co., Ltd. Kaoru Yokoyama received honorariums from Abbvie GK, EA Pharma Co., Ltd., Gilead Sciences Inc., and Takeda Pharmaceutical Co., Ltd. Makoto Naganuma received honorariums from EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical KK., Abbvie GK., JIMRO Co., Ltd., Pfizer Inc., Gilead Sciences Inc., and Takeda Pharmaceutical Co., Ltd., research grants from Kyorin Pharmaceutical Co., Ltd. Mitsubishi Tanabe Pharma Co., Abbvie GK., and Miyarisan Pharmaceutical Co., Ltd., and fees paid for writing a pamphlet from Alfresa Pharma Co. Ltd., Masayuki Saruta received honorariums from Abbvie GK., Takeda Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Gilead Sciences Inc., Janssen Pharmaceutical K.K, Kissei Pharmaceutical Co., Ltd., Viatris Pharmaceutical Co., Ltd., and Nobel Pharma Co. Ltd., research grants from Abbvie GK. CMO Co. Ltd. and PPD-SNBL KK., and scholarship grants from Abbvie GK., Zeria Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., and Kissei Pharmaceutical Co., Ltd. Hiroshi Seno received honorariums from Eisai Co., Ltd., and scholarship grants from Mitsubishi Tanabe Pharma Co. All other authors have no conflicts of interest.

Figures

**Fig. 2**
Serum anti-integrin αvβ6 antibody titers in patients with UC, CD, and OGDs. V6 Ab titers were measured using an enzyme-linked immunosorbent assay kit. The cut-off value of 1.64 U/mL, defined as the mean + 3SDs of 83 serum samples from healthy volunteers as determined by the manufacturer, is indicated by a dashed line. n total number of patients in each group. UC ulcerative colitis, CD Crohn’s disease, *OGDs* other gastrointestinal diseases

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Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

Affiliations

Anti-integrin αvβ6 antibody as a biomarker for diagnosing ulcerative colitis: a nationwide multicenter validation study

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical