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


RESULTS
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
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.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. hisamachi@a7.keio.jp
Tadakazu
T
Hisamatsu
Susumu
S
Okamoto
Masaki
M
Hashimoto
Takahiko
T
Muramatsu
Ayatoshi
A
Andou
Michihide
M
Uo
Mina T
MT
Kitazume
Katsuyoshi
K
Matsuoka
Tomoharu
T
Yajima
Nagamu
N
Inoue
Takanori
T
Kanai
Haruhiko
H
Ogata
Yasushi
Y
Iwao
Minoru
M
Yamakado
Ryosei
R
Sakai
Nobukazu
N
Ono
Toshihiko
T
Ando
Manabu
M
Suzuki
Toshifumi
T
Hibi
D000328:Adult; D000596:Amino Acids / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006639:Histidine / Q000097:blood; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000097:blood
D000596:Amino Acids; D015415:Biomarkers; D006639:Histidine; D014364:Tryptophan