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Antibodies to Crohn’s disease peptide 353 as a diagnostic marker for pediatric Crohn’s disease: a prospective multicenter study in Japan

  • Original Article—Alimentary Tract
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Abstract

Background

Various serologic markers such as anti-glycoprotein 2 antibodies and anti-Saccharomyces cerevisiae antibodies have been reported to be diagnostically useful in Crohn’s disease. Mitsuyama et al. reported that antibodies to Crohn’s disease peptide 353, a newly proposed serologic marker, were more useful in Japanese adults than anti-Saccharomyces. We addressed the same issue in Japanese children and adolescents.

Methods

Prospectively enrolled subjects under 17 years old assessed and treated at 12 pediatric centers in Japan included groups with Crohn’s disease, ulcerative colitis, other intestinal diseases, or good health. The 3 serum markers were analyzed by enzyme-linked immunosorbent assays.

Results

Enrolled subjects, numbering 367, included 120 with Crohn’s disease, 148 with ulcerative colitis, 56 with other intestinal diseases, and 43 healthy subjects. In Crohn’s disease, anti-Crohn’s disease peptide 353, anti-glycoprotein 2, and anti-Saccharomyces concentrations (median, 2.25, 3.0, and 8.9 U/mL) were significantly greater than in ulcerative colitis (1.1, 1.9, and 3.4; all P < 0.001), other intestinal diseases (1.1, 1.85, and 2.95; all P < 0.001), and healthy controls (1.1, 1.7, and 2.8; all P < 0.001), respectively. At 95% specificity, sensitivity of anti-Crohn’s disease peptide (45.0%) was significantly higher than for anti-glycoprotein 2 (30.8%; P < 0.05) or anti-Saccharomyces (26.7%; P < 0.01).

Conclusions

Anti-Crohn’s disease peptide 353 proved more useful for diagnosis of Crohn’s disease in Japanese children than the other 2 markers. To our knowledge, this is the first pediatric report to that effect.

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Abbreviations

IBD:

Inflammatory bowel disease

CD:

Crohn’s disease

UC:

Ulcerative colitis

IBDU:

Inflammatory bowel disease unclassified

ANCA:

Antineutrophil cytoplasmic antibodies

ASCA:

Anti-Saccharomyces cerevisiae antibodies

GP2:

Anti-glycoprotein 2 antibodies

ACP353:

Antibodies to Crohn’s disease peptide 353

MBL:

Medical & Biological Laboratories

IC:

Intestinal disease control

XIAP:

X-linked inhibitor of apoptosis

IBS:

Irritable bowel syndrome

HC:

Healthy control

PCDAI:

Pediatric Crohn’s Disease Activity Index

PUCAI:

Pediatric Ulcerative Colitis Activity Index

ELISA:

Enzyme-linked immunosorbent assay

IgG:

Immunoglobulin G

PBS:

Phosphate-buffered saline

ROC:

Receiver operating characteristic

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Acknowledgements

The authors thank all participating patients, their families, and physicians for collaborating in data collection.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 8300011, Japan

    Tatsuki Mizuochi, Yugo Takaki, Ken-ichiro Konishi, Jun Ishihara & Yushiro Yamashita

  2. Division of Gastroenterology, National Center for Child Health and Development, Tokyo, Japan

    Katsuhiro Arai

  3. Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan

    Takahiro Kudo

  4. Division of Gastroenterology and Hepatology, Saitama Children’s Medical Center, Saitama, Japan

    Ryusuke Nambu

  5. Department of Pediatrics, Osaka General Medical Center, Osaka, Japan

    Hitoshi Tajiri

  6. Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka, Japan

    Tomoki Aomatsu

  7. Department of Infection and Immunology, Aichi Children’s Health and Medical Center, Obu, Aichi, Japan

    Naoki Abe

  8. Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan

    Toshihiko Kakiuchi

  9. Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Kunio Hashimoto

  10. Department of Pediatric Hepatology and Gastroenterology, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan

    Tsuyoshi Sogo

  11. Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo, Japan

    Michiko Takahashi

  12. Department of Gastroenterology and Endocrinology, Osaka Women’s and Children’s Hospital, Osaka, Japan

    Yuri Etani

  13. Biostatistics Center, Kurume University School of Medicine, Kurume, Japan

    Hitoshi Obara & Tatsuyuki Kakuma

  14. Medical & Biological Laboratories, Nagoya, Japan

    Shunsuke Kurei

  15. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan

    Keiichi Mitsuyama

Authors
  1. Tatsuki Mizuochi
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  2. Katsuhiro Arai
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  3. Takahiro Kudo
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  4. Ryusuke Nambu
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  5. Hitoshi Tajiri
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  6. Tomoki Aomatsu
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  7. Naoki Abe
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  8. Toshihiko Kakiuchi
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  9. Kunio Hashimoto
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  11. Michiko Takahashi
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  12. Yuri Etani
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  13. Yugo Takaki
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  14. Ken-ichiro Konishi
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  15. Jun Ishihara
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  16. Hitoshi Obara
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  17. Tatsuyuki Kakuma
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  18. Shunsuke Kurei
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  19. Yushiro Yamashita
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  20. Keiichi Mitsuyama
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Contributions

Concept and design of study, TM and KM; acquisition of serum samples and data, TM, KA, TaK, RN, HT, TA, NA, ToK, KH, TS, MT, YE, YT, KK, JI, YY, and KM; serum antibody assays, SK; analysis and interpretation of data, TM, HO, TaK, and KM; drafting of the article, TM; refining the draft, TM, TaK, YY, and KM; critical review and approval of the draft, all authors.

Corresponding author

Correspondence to Tatsuki Mizuochi.

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Conflict of interest

Shunsuke Kurei is an employee of Medical & Biological Laboratories, a collaborating company where the serum antibody assays were performed in a blinded manner without interpretation of data. Toagosei Co., Ltd. and Kurume University have applied to register a patent concerning the ACP353 test. The title of the invention is: Crohn's disease antibody epitope peptide and reagent for testing Crohn's disease. Applicable registration numbers are JP4597132; EP 1780215; US 7,985,831; KR 10–1159626; and ZL200910159881.0(CN).

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Supplementary file1 (DOCX 17 kb)

535_2019_1661_MOESM2_ESM.jpg

Supplementary Figure 1. ROC curves for ACP353, GP2, and ASCA among IBD, IBS, and infectious enterocolitis. Areas under receiver operating characteristic (ROC) curves for antibodies to Crohn’s disease peptide 353 (ACP353)/anti-glycoprotein 2 antibodies (GP2)/anti-Saccharomyces cerevisiae antibodies (ASCA) in distinguishing inflammatory bowel disease (IBD) including Crohn’s disease (CD), ulcerative colitis (UC), IBD-unclassified, Behçet's disease, and X-linked inhibitor of apoptosis deficiency from irritable bowel syndrome (IBS) [A]; IBD from infectious enterocolitis [B]; and CD from UC [C] were 0.66/0.52/0.61, 0.53/0.67/0.68, and 0.78/0.72/0.72, respectively (JPG 3485 kb)

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Mizuochi, T., Arai, K., Kudo, T. et al. Antibodies to Crohn’s disease peptide 353 as a diagnostic marker for pediatric Crohn’s disease: a prospective multicenter study in Japan. J Gastroenterol 55, 515–522 (2020). https://doi.org/10.1007/s00535-019-01661-y

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