Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease

Tadakazu Hisamatsu, Susumu Okamoto, Masaki Hashimoto, Takahiko Muramatsu, Ayatoshi Andou, Michihide Uo, Mina T. Kitazume, Katsuyoshi Matsuoka, Tomoharu Yajima, Nagamu Inoue, Takanori Kanai, Haruhiko Ogata, Yasushi Iwao, Minoru Yamakado, Ryosei Sakai, Nobukazu Ono, Toshihiko Ando, Manabu Suzuki, Toshifumi Hibi

Research output: Contribution to journalArticle

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Abstract

Background: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). Methodology and Principal Findings: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898-0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r s = 0.592, 95%CI: 0.385-0.742, p<0.001) or UC (r s = 0.598, 95%CI: 0.452-0.713, p<0.001), respectively. Conclusions and Significance: In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease.

Original languageEnglish
Article numbere31131
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - 2012 Jan 31

Fingerprint

Crohn disease
inflammatory bowel disease
colitis
Biomarkers
Ulcerative Colitis
Inflammatory Bowel Diseases
Crohn Disease
biomarkers
confidence interval
Plasmas
Amino Acids
amino acids
Confidence Intervals
Area Under Curve
remission
pathophysiology
digestive system diseases
histidine
Histidine
ROC Curve

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. / Hisamatsu, Tadakazu; Okamoto, Susumu; Hashimoto, Masaki; Muramatsu, Takahiko; Andou, Ayatoshi; Uo, Michihide; Kitazume, Mina T.; Matsuoka, Katsuyoshi; Yajima, Tomoharu; Inoue, Nagamu; Kanai, Takanori; Ogata, Haruhiko; Iwao, Yasushi; Yamakado, Minoru; Sakai, Ryosei; Ono, Nobukazu; Ando, Toshihiko; Suzuki, Manabu; Hibi, Toshifumi.

In: PLoS One, Vol. 7, No. 1, e31131, 31.01.2012.

Research output: Contribution to journalArticle

Hisamatsu, T, Okamoto, S, Hashimoto, M, Muramatsu, T, Andou, A, Uo, M, Kitazume, MT, Matsuoka, K, Yajima, T, Inoue, N, Kanai, T, Ogata, H, Iwao, Y, Yamakado, M, Sakai, R, Ono, N, Ando, T, Suzuki, M & Hibi, T 2012, 'Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease', PLoS One, vol. 7, no. 1, e31131. https://doi.org/10.1371/journal.pone.0031131
Hisamatsu, Tadakazu ; Okamoto, Susumu ; Hashimoto, Masaki ; Muramatsu, Takahiko ; Andou, Ayatoshi ; Uo, Michihide ; Kitazume, Mina T. ; Matsuoka, Katsuyoshi ; Yajima, Tomoharu ; Inoue, Nagamu ; Kanai, Takanori ; Ogata, Haruhiko ; Iwao, Yasushi ; Yamakado, Minoru ; Sakai, Ryosei ; Ono, Nobukazu ; Ando, Toshihiko ; Suzuki, Manabu ; Hibi, Toshifumi. / Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. In: PLoS One. 2012 ; Vol. 7, No. 1.
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AU - Hisamatsu, Tadakazu

AU - Okamoto, Susumu

AU - Hashimoto, Masaki

AU - Muramatsu, Takahiko

AU - Andou, Ayatoshi

AU - Uo, Michihide

AU - Kitazume, Mina T.

AU - Matsuoka, Katsuyoshi

AU - Yajima, Tomoharu

AU - Inoue, Nagamu

AU - Kanai, Takanori

AU - Ogata, Haruhiko

AU - Iwao, Yasushi

AU - Yamakado, Minoru

AU - Sakai, Ryosei

AU - Ono, Nobukazu

AU - Ando, Toshihiko

AU - Suzuki, Manabu

AU - Hibi, Toshifumi

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N2 - Background: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). Methodology and Principal Findings: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898-0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r s = 0.592, 95%CI: 0.385-0.742, p<0.001) or UC (r s = 0.598, 95%CI: 0.452-0.713, p<0.001), respectively. Conclusions and Significance: In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease.

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