Skip to main content

Advertisement

SpringerLink
Log in

New chemiluminescent enzyme immunoassay for quantitative measurement of Mac-2 binding protein glycosylation isomer in chronic liver disease

  • Original Article―Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

This study aimed to evaluate the quantitative measurement of Mac-2 binding protein glycosylation isomer (M2BPGi) levels using the new chemiluminescent enzyme immunoassay.

Methods

The data of a total of 347 patients with hepatitis C virus (HCV) infection and 150 health volunteers from 13 locations in Japan were evaluated. The quantitative system for measuring M2BPGi-Qt levels was based on a new chemiluminescent enzyme immunoassay. We evaluated the reproducibility and quantitation range in quantitative M2BPGi-Qt measurement. We also investigated the confidence ratio of M2BPGi-Qt levels measured by the new quantitative system to M2BPGi levels measured by the current semi-quantitative system for validating the clinical utility of the new method.

Results

The reproducibility of M2BPGi-Qt in HCV samples with negative, positive 1+, and positive 2+ was 0.77 ± 0.02 AU/mL, 2.25 ± 0.03 AU/mL, and 6.55 ± 0.21 AU/mL, respectively, and the corresponding coefficient of variation (CV)s were 2.1%, 1.3%, and 3.2%, respectively. The range of quantification assessment resulted that all CVs showed less than 5% in investigated range. Sample stability testing found that the mean percentage difference between the pre- and post-storage values of 6 samples ranged between 96.2 and 103.9%. The correlation coefficient between M2BPGi and M2BPGi-Qt in patients with HCV and the healthy volunteers was 0.986 and 0.991, respectively. M2BPGi-Qt could be quantitatively assessed in a patient with over 20 C.O.I.

Conclusion

Compared with qualitative methods, the M2BPGi quantitative measurement system could provide a numerical value unaffected by interpretation bias, and measurements are more precise at high M2BPGi levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ginès P, Krag A, Abraldes JG, et al. Liver cirrhosis. Lancet. 2021;398:1359–76.

    Article  PubMed  Google Scholar 

  2. Rockey DC, Caldwell SH, Goodman ZD, et al. Liver biopsy. Hepatology. 2009;49:1017–44.

    Article  PubMed  Google Scholar 

  3. Mózes FE, Lee JA, Selvaraj EA, et al. Diagnostic accuracy of non-invasive tests for advanced fibrosis in patients with NAFLD: an individual patient data meta-analysis. Gut. 2022;71:1006–19.

    Article  PubMed  Google Scholar 

  4. Toshima T, Shirabe K, Ikegami T, et al. A novel serum marker, glycosylated Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP), for assessing liver fibrosis. J Gastroenterol. 2015;50:76–84.

    Article  CAS  PubMed  Google Scholar 

  5. Shirabe K, Bekki Y, Gantumur D, et al. Mac-2 binding protein glycan isomer (M2BPGi) is a new serum biomarker for assessing liver fibrosis: more than a biomarker of liver fibrosis. J Gastroenterol. 2018;53:819–26.

    Article  CAS  PubMed  Google Scholar 

  6. Abe M, Miyake T, Kuno A, et al. Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease. J Gastroenterol. 2015;50:776–84.

    Article  CAS  PubMed  Google Scholar 

  7. Umemura T, Joshita S, Sekiguchi T, et al. Serum wisteria floribunda agglutinin-positive Mac-2-binding protein level predicts liver fibrosis and prognosis in primary biliary cirrhosis. Am J Gastroenterol. 2015;110:857–64.

    Article  CAS  PubMed  Google Scholar 

  8. Narimatsu H. Development of M2BPGi: a novel fibrosis serum glyco-biomarker for chronic hepatitis/cirrhosis diagnostics. Expert Rev Proteomics. 2015;12:683–93.

    Article  CAS  PubMed  Google Scholar 

  9. Matsumoto K, Yoshimoto J, Sugo H, et al. Relationship between the histological degrees of hepatitis and the postoperative recurrence of hepatocellular carcinoma in patients with hepatitis C. Hepatol Res. 2002;23:196–201.

    Article  PubMed  Google Scholar 

  10. Ueno T, Kodama T, Noguchi Y, et al. Serum Mac-2-binding protein (M2BPGi) as a marker of chronological liver fibrosis in biliary atresia patients with cirrhosis. Pediatr Surg Int. 2019;35:1065–70.

    Article  PubMed  Google Scholar 

  11. Mak LY, Wong DK, Seto WK, et al. Correlation of serum Mac-2-binding protein glycosylation isomer (M2BPGi) and liver stiffness in chronic hepatitis B infection. Hepatol Int. 2019;13:148–56.

    Article  PubMed  Google Scholar 

  12. Alkhouri N, Johnson C, Adams L, et al. Serum Wisteria floribunda agglutinin-positive Mac-2-binding protein levels predict the presence of fibrotic nonalcoholic steatohepatitis (NASH) and NASH cirrhosis. PLoS ONE. 2018;13: e0202226.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shao X, Uojima H, Setsu T, et al. Usefulness of autotaxin for the complications of liver cirrhosis. World J Gastroenterol. 2020;26:97–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Migita K, Horai Y, Kozuru H, et al. Serum cytokine profiles and Mac-2 binding protein glycosylation isomer (M2BPGi) level in patients with autoimmune hepatitis. Medicine (Baltimore). 2018;97: e13450.

    Article  CAS  PubMed  Google Scholar 

  15. Morio K, Imamura M, Daijo K, et al. Wisteria floribunda agglutinin positive Mac-2-binding protein level increases in patients with acute liver injury. J Gastroenterol. 2017;52:1252–7.

    Article  CAS  PubMed  Google Scholar 

  16. Bekki Y, Yoshizumi T, Shimoda S, et al. Hepatic stellate cells secreting WFA+ M2BP: its role in biological interactions with Kupffer cells. J Gastroenterol Hepatol. 2017;32:1387–93.

    Article  CAS  PubMed  Google Scholar 

  17. Singh T, Allende DS, McCullough AJ. Assessing liver fibrosis without biopsy in patients with HCV or NAFLD. Cleve Clin J Med. 2019;86:179–86.

    Article  PubMed  Google Scholar 

  18. Medvedev R, Ploen D, Hildt E. HCV and oxidative stress: implications for HCV life cycle and HCV-associated pathogenesis. Oxid Med Cell Longev. 2016;2016:9012580.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sirbe C, Simu G, Szabo I, et al. Pathogenesis of autoimmune hepatitis-cellular and molecular mechanisms. Int J Mol Sci. 2021;22:13578.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sucher E, Sucher R, Gradistanac T, et al. Autoimmune hepatitis-immunologically triggered liver pathogenesis-diagnostic and therapeutic strategies. J Immunol Res. 2019;2019:9437043.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Joshita S, Umemura T, Usami Y, et al. Serum autotaxin is a useful disease progression marker in patients with primary biliary cholangitis. Sci Rep. 2018;8:8159.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nakagawa M, Nawa N, Takeichi E, et al. Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs. J Gastroenterol. 2020;55:990–9.

    Article  CAS  PubMed  Google Scholar 

  23. Tangvoraphonkchai K, Suttichaimongkol T, Kularbkaew C, et al. Application of Mac-2 binding protein glycosylation isomer as a non-invasive biomarker for probing liver disease. Sci Rep. 2022;12:6757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the SATISTA Corporation for assistance with the statistical analyses.

Funding

This study was supported by Sysmex Corporation.

Author information

Authors and Affiliations

  1. Department of Genome Medical Sciences Project, Research Institute, National Center for Global Health and Medicine, 1-7-1, Kohnodai, Ichikawa, Chiba, 272-8516, Japan

    Haruki Uojima, Masaya Sugiyama & Masashi Mizokami

  2. Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    Haruki Uojima, Hisashi Hidaka & Chika Kusano

  3. Department of Reagent Engineering, Sysmex Corporation, Kobe, Japan

    Kadzuki Nakabayashi, Takuya Kyoutou, Koji Ueda & Yoichi Takahama

  4. Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Ōmura, Japan

    Kazumi Yamasaki & Hiroshi Yatsuhashi

  5. Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma, Japan

    Norihiro Ishii & Ken Shirabe

  6. Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan

    Nobuharu Tamaki & Masayuki Kurosaki

  7. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Asahi-Machi, Kurume, Fukuoka, Japan

    Keisuke Amano & Takumi Kawaguchi

  8. Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Akinobu Taketomi & Satoru Joshita

  9. Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine. Asahi, Matsumoto, Japan

    Takeji Umemura

  10. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan

    Miyako Murakawa & Yasuhiro Asahina

  11. Department of Liver Disease Control, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan

    Yasuhiro Asahina

  12. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Takanori Suzuki & Kentaro Matsuura

  13. Division of Hepatobiliary and Pancreatic Disease, Department of Gastroenterology, Hyogo Medical University, Nishinomiya, Japan

    Takashi Nishimura & Hiroko Iijima

  14. Department of Gastroenterology, Aichi Medical University, Aichi, Japan

    Kazumasa Sakamoto & Kiyoaki Ito

  15. Department of Hepatology and Pancreatology, Kawasaki Medical University, Kurashiki, Japan

    Sohji Nishina & Keisuke Hino

  16. Digestive Disease Center, Shunan Memorial Hospital, Kudamatsu, Japan

    Keisuke Hino

  17. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan

    Hidenori Toyoda

  18. Kurume University, Kurume, Japan

    Masayoshi Kage

Authors
  1. Haruki Uojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kadzuki Nakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazumi Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masaya Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norihiro Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ken Shirabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takuya Kyoutou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Koji Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yoichi Takahama
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nobuharu Tamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masayuki Kurosaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hisashi Hidaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chika Kusano
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Keisuke Amano
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Takumi Kawaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Akinobu Taketomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Satoru Joshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Takeji Umemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Miyako Murakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Yasuhiro Asahina
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Takanori Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Kentaro Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Takashi Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Hiroko Iijima
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Kazumasa Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Kiyoaki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Sohji Nishina
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Keisuke Hino
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Hidenori Toyoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Hiroshi Yatsuhashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Masayoshi Kage
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Masashi Mizokami
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

NK and MK collected and analyzed the data; HU and MM drafted the manuscript; M K designed and supervised the study; KY, MS, KS offered technical or material support; all authors have read and approved the final version to be published.

Corresponding author

Correspondence to Haruki Uojima.

Ethics declarations

Conflict of interest

Takeji Umemura received a lecture fee from AbbVie GK, Gilead Sciences and and a research grant from AbbVie GK, Eisai Co., Otsuka Pharmaceutical Co., Tosoh Co. Masayuki Kurosaki received a lecture fee from AbbVie, Eisai, Chugai, AstraZeneca, Lilly, Takeda Co. Masashi Mizokami received a lecture fee from Sysmec Co. Yasuhiro Asahina received a lecture fee from Fujirebi Inc, Abbott Japan LLC. Takumi Kawaguchi received lecture fees from Taisho Pharmaceutical Co., Kowa Company., Otsuka Pharmaceutical Co., Eisai Co., Janssen Pharmaceutical K.K., AbbVie GK., ASKA Pharmaceutical Co., EA Pharma Co. and a research grant from Eisai Co., Ltd.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 22 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Uojima, H., Nakabayashi, K., Yamasaki, K. et al. New chemiluminescent enzyme immunoassay for quantitative measurement of Mac-2 binding protein glycosylation isomer in chronic liver disease. J Gastroenterol 58, 1252–1260 (2023). https://doi.org/10.1007/s00535-023-02043-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-023-02043-1

Keywords

Search

Navigation