Limits...
Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission.

Hisamatsu T, Ono N, Imaizumi A, Mori M, Suzuki H, Uo M, Hashimoto M, Naganuma M, Matsuoka K, Mizuno S, Kitazume MT, Yajima T, Ogata H, Iwao Y, Hibi T, Kanai T - PLoS ONE (2015)

Bottom Line: Ulcerative colitis (UC) is characterized by chronic intestinal inflammation.The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005).Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

ABSTRACT
Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus

Trends of cumulative relapse ratio for each quartile by unadjusted plasma histidine level (A), unadjusted CRP level (B), unadjusted TNF-alpha level (C), normalized histidine level (D), normalized CRP level (E), and normalized TNF-alpha level (F).Blue: 1st quartile, purple: 2nd quartile, pink: 3rd quartile, red: 4th quartile.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608807&req=5

pone.0140716.g003: Trends of cumulative relapse ratio for each quartile by unadjusted plasma histidine level (A), unadjusted CRP level (B), unadjusted TNF-alpha level (C), normalized histidine level (D), normalized CRP level (E), and normalized TNF-alpha level (F).Blue: 1st quartile, purple: 2nd quartile, pink: 3rd quartile, red: 4th quartile.

Mentions: For Cox regression analysis, three types of PFAA profiles were used as described in Materials and Methods. Under any conditions of Cox regression analysis, significant HRs were observed only for histidine (p<0.05) even after adjustment and normalization for relapse of UC, while with unadjusted raw data, and gender- and age-adjusted data, significant HRs were observed also for glutamate (p<0.05) (Table 2). The concentration of histidine was inversely correlated with relapse rate of UC (β = −0.2687) (Table 2). In contrast, there were no significant HRs under any conditions for C-reactive protein (CRP; p>0.491) and TNF-alpha (p>0.0625) (Table 2). To confirm the negative dependency of plasma histidine concentration for relapse, Kaplan—Meier curve of each quartile was plotted using raw data, and gender- and age-adjusted data. In any case, a significant negative trend in relapse rate for UC was observed in plasma histidine level (p = 0.0136) (Fig 3A), whereas no significant trend was observed in CRP (p = 0.8448, unadjusted; p = 0.2758, adjusted) and TNF-alpha levels (p = 0.50, unadjusted; p = 0.12, adjusted) (Fig 3B, 3C, 3E and 3F). Note that dependency on concentration was observed in gender- and age-adjusted data more clearly (p = 0.0005) (Fig 3D), suggesting that plasma histidine concentration is affected by gender and/or age in UC patients. The relapse rate of the first quartile within 1 year after remission was ~2.55 times higher than that of the fourth quartile (95% confidence interval: 1.41–4.62) (Table 3).


Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission.

Hisamatsu T, Ono N, Imaizumi A, Mori M, Suzuki H, Uo M, Hashimoto M, Naganuma M, Matsuoka K, Mizuno S, Kitazume MT, Yajima T, Ogata H, Iwao Y, Hibi T, Kanai T - PLoS ONE (2015)

Trends of cumulative relapse ratio for each quartile by unadjusted plasma histidine level (A), unadjusted CRP level (B), unadjusted TNF-alpha level (C), normalized histidine level (D), normalized CRP level (E), and normalized TNF-alpha level (F).Blue: 1st quartile, purple: 2nd quartile, pink: 3rd quartile, red: 4th quartile.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608807&req=5

pone.0140716.g003: Trends of cumulative relapse ratio for each quartile by unadjusted plasma histidine level (A), unadjusted CRP level (B), unadjusted TNF-alpha level (C), normalized histidine level (D), normalized CRP level (E), and normalized TNF-alpha level (F).Blue: 1st quartile, purple: 2nd quartile, pink: 3rd quartile, red: 4th quartile.
Mentions: For Cox regression analysis, three types of PFAA profiles were used as described in Materials and Methods. Under any conditions of Cox regression analysis, significant HRs were observed only for histidine (p<0.05) even after adjustment and normalization for relapse of UC, while with unadjusted raw data, and gender- and age-adjusted data, significant HRs were observed also for glutamate (p<0.05) (Table 2). The concentration of histidine was inversely correlated with relapse rate of UC (β = −0.2687) (Table 2). In contrast, there were no significant HRs under any conditions for C-reactive protein (CRP; p>0.491) and TNF-alpha (p>0.0625) (Table 2). To confirm the negative dependency of plasma histidine concentration for relapse, Kaplan—Meier curve of each quartile was plotted using raw data, and gender- and age-adjusted data. In any case, a significant negative trend in relapse rate for UC was observed in plasma histidine level (p = 0.0136) (Fig 3A), whereas no significant trend was observed in CRP (p = 0.8448, unadjusted; p = 0.2758, adjusted) and TNF-alpha levels (p = 0.50, unadjusted; p = 0.12, adjusted) (Fig 3B, 3C, 3E and 3F). Note that dependency on concentration was observed in gender- and age-adjusted data more clearly (p = 0.0005) (Fig 3D), suggesting that plasma histidine concentration is affected by gender and/or age in UC patients. The relapse rate of the first quartile within 1 year after remission was ~2.55 times higher than that of the fourth quartile (95% confidence interval: 1.41–4.62) (Table 3).

Bottom Line: Ulcerative colitis (UC) is characterized by chronic intestinal inflammation.The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005).Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

ABSTRACT
Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus