Intestinal Research

Masaki Iimuro

2 Articles

IBD

Usefulness of fecal calprotectin by monoclonal antibody testing in adult Japanese with inflammatory bowel diseases: a prospective multicenter study: Shiro Nakamura, Hirotsugu Imaeda, Hiroki Nishikawa, Masaki Iimuro, Minoru Matsuura, Hideo Oka, Junsuke Oku, Takako Miyazaki, Hirohito Honda, Kenji Watanabe, Hiroshi Nakase, Akira Andoh; Intest Res 2018;16(4):554-562. Published online October 10, 2018; DOI: https://doi.org/10.5217/ir.2018.00027

Background/Aims
Noninvasive objective monitoring is advantageous for optimizing treatment strategies in patients inflammatory bowel disease (IBD). Fecal calprotectin (FCP) is superior to traditional biomarkers in terms of assessing the activity in patients with IBD. However, there are the differences among several FCP assays in the dynamics of FCP. In this prospective multicenter trial, we investigated the usefulness of fecal FCP measurements in adult Japanese patients with IBD by reliable enzyme immunoassay using a monoclonal antibody.
Methods
We assessed the relationship between FCP levels and disease or endoscopic activity in patients with ulcerative colitis (UC, n=64) or Crohn’s disease (CD, n=46) compared with healthy controls (HCs, n=64).
Results
FCP levels in UC patients strongly correlated with the Disease Activity Index (rs=0.676, P<0.0001) and Mayo endoscopic subscore (MES; rs=0.677, P<0.0001). FCP levels were significantly higher even in patients with inactive UC or CD compared with HCs (P=0.0068, P<0.0001). The optimal cutoff value between MES 1 and 2 exhibited higher sensitivity (94.1%). FCP levels were significantly higher in active UC patients than in inactive patients (P<0.001), except those with proctitis. The Crohn’s Disease Activity Index tended to correlate with the FCP level (rs=0.283, P=0.0565).
Conclusions
Our testing method using a monoclonal antibody for FCP was well-validated and differentiated IBD patients from HCs. FCP may be a useful biomarker for objective assessment of disease activity in adult Japanese IBD patients, especially those with UC.

Citations

Citations to this article as recorded by

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NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases: Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura; Intest Res 2017;15(3):328-337. Published online June 12, 2017; DOI: https://doi.org/10.5217/ir.2017.15.3.328

Abstract PDF PubReader ePub

<b>Background/Aims</b><br/>

Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).

Methods

One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.

Results

None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose. NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, FTO p.Ala134Thr, and RUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.

Conclusions

Of the 5 variants investigated, NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.

Citations

Citations to this article as recorded by

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A systematic review of aspects of NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression
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Time to incorporate preemptive NUDT15 testing before starting thiopurines in inflammatory bowel disease in Asia and beyond: a review
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101 Download
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