Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease

Yasutomi, Eriko; Inokuchi, Toshihiro; Hiraoka, Sakiko; Takei, Kensuke; Igawa, Shoko; Yamamoto, Shumpei; Ohmori, Masayasu; Oka, Shiro; Yamasaki, Yasushi; Kinugasa, Hideaki; Takahara, Masakazu; Harada, Kensuke; Furukawa, Masaki; Itoshima, Kouichi; Okada, Ken; Otsuka, Fumio; Tanaka, Takehiro; Mitsuhashi, Toshiharu; Kato, Jun; Okada, Hiroyuki

doi:10.1038/s41598-021-90441-x

Cited by 55 publications

(50 citation statements)

References 41 publications

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“…Yasutomi et al reported that in patients with UC, the area under the curve (AUC) of LRG in patients who received anti-TNF-α agents was not superior to that of patients who did not receive it. In patients with CD, the AUC of LRG in patients who received anti-TNF-α agents was higher than that in patients who did not receive it [135].…”

Section: Effects Of Anti-tnf-α Agents On Lrg Levelsmentioning

confidence: 77%

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Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

Wagatsuma

Yokoyama

Nakase

2021

Life

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The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Endoscopy is the gold standard to assess the condition of IBD. The problem with this procedure is that the burden and cost on the patient are high. Therefore, the identification of a reliable biomarker to replace endoscopy is desired. Biomarkers are used in various situations such as diagnosis of IBD, evaluation of disease activity, prediction of therapeutic effect, and prediction of relapse. C-reactive protein and fecal calprotectin have a lot of evidence as objective biomarkers of disease activity in IBD. The usefulness of the fecal immunochemical test, serum leucine-rich glycoprotein, and urinary prostaglandin E major metabolite have also been reported. Herein, we comprehensively review the usefulness and limitations of biomarkers that can be used in daily clinical practice regarding IBD. To date, no biomarker is sufficiently accurate to replace endoscopy; however, it is important to understand the characteristics of each biomarker and use the appropriate biomarker at the right time in daily clinical practice.

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Section: Effects Of Anti-tnf-α Agents On Lrg Levelsmentioning

confidence: 77%

“…The reason for the difference from the previous study was a large number of enrolled patients with low disease activity. Fecal markers could be preferable for patients with IBD with low disease activity compared to LRG [135].…”

Section: Evaluation Of Disease Activity By Lrgmentioning

confidence: 99%

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

Wagatsuma

Yokoyama

Nakase

2021

Life

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“…reported that expression of the Lrg1 gene, amongst others, mediates the proliferation of human colon epithelial cells in vitro following stimulation with IL-22 [ 61 ]. As IL-22 is a pro-inflammatory cytokine abundant in patients with ulcerative colitis (UC) that feature an extensively compromised intestinal mucosa, the hypothesis that LRG1 might orchestrate the correct renewal of damaged epithelial cells [ 62 ] is certainly very intriguing and in line with other observations. In fact, Pickert et al .…”

Section: Reviewmentioning

confidence: 93%

LRG1: an emerging player in disease pathogenesis

et al. 2022

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The secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) was first described as a key player in pathogenic ocular neovascularization almost a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. The purpose of this review is to provide, for the first time, a comprehensive overview of the LRG1 literature considering its role in health and disease. Although LRG1 is constitutively expressed by hepatocytes and neutrophils, Lrg1−/− mice show no overt phenotypic abnormality suggesting that LRG1 is essentially redundant in development and homeostasis. However, emerging data are challenging this view by suggesting a novel role for LRG1 in innate immunity and preservation of tissue integrity. While our understanding of beneficial LRG1 functions in physiology remains limited, a consistent body of evidence shows that, in response to various inflammatory stimuli, LRG1 expression is induced and directly contributes to disease pathogenesis. Its potential role as a biomarker for the diagnosis, prognosis and monitoring of multiple conditions is widely discussed while dissecting the mechanisms underlying LRG1 pathogenic functions. Emphasis is given to the role that LRG1 plays as a vasculopathic factor where it disrupts the cellular interactions normally required for the formation and maintenance of mature vessels, thereby indirectly contributing to the establishment of a highly hypoxic and immunosuppressive microenvironment. In addition, LRG1 has also been reported to affect other cell types (including epithelial, immune, mesenchymal and cancer cells) mostly by modulating the TGFβ signalling pathway in a context-dependent manner. Crucially, animal studies have shown that LRG1 inhibition, through gene deletion or a function-blocking antibody, is sufficient to attenuate disease progression. In view of this, and taking into consideration its role as an upstream modifier of TGFβ signalling, LRG1 is suggested as a potentially important therapeutic target. While further investigations are needed to fill gaps in our current understanding of LRG1 function, the studies reviewed here confirm LRG1 as a pleiotropic and pathogenic signalling molecule providing a strong rationale for its use in the clinic as a biomarker and therapeutic target.

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“…Second, there is no comparison with LRG. LRG is a biomarker of UC that can be measured in blood samples as well as in CRP [10,11]. Thus, LRG is a marker that is expected to be widely used in many facilities in the future, because reagents and equipment are easily available, and measurement results can be determined on the same day of consultation.…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between PGE-MUM and endoscopic scores was previously reported [8,9]. Recently, leucine-rich 2 glycoprotein (LRG) using blood samples has also been reported to be a useful biomarker in UC, and is now being used in clinical practice [10,11]. Although various biomarkers for UC have emerged, the identification of simple markers that are inexpensive and can be measured at any institution would be of great help in the objective evaluation of UC in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Lymphocyte-to-Monocyte Ratio as a Marker for Endoscopic Activity in Ulcerative Colitis

Ishida

Takahashi

Asai

et al. 2021

Immuno

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Leukocyte subtypes can be used to evaluate the severity of ulcerative colitis (UC). In this study, we examined the relationship between the lymphocyte-to-monocyte ratio (LMR) and the Mayo endoscopic score (MES) in assessing endoscopic activity in UC. Eighty-nine samples of leukocyte subtypes and biomarkers, including fecal calprotectin (FC), the fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP), from 71 patients with UC were retrospectively investigated, along with the MES. The MES was significantly correlated with the LMR, FC, the FIT, and CRP. There were significant differences in the LMR, FC, the FIT, and CRP between groups with an MES < 1 and >2 (p = 0.001, p = 0.003, p < 0.001, and p < 0.001, respectively). In the receiver operating characteristic (ROC) analysis for predicting mucosal healing (MES 0 or 1), the areas under the curve (AUCs) for the LMR, FC, the FIT, and CRP, were 0.712, 0.860, 0.908, and 0.796, respectively. In the analysis of patients without immunomodulators, the correlation of the MES with the LMR and CRP was significant. The LMR can be used to assess endoscopic activity in UC, particularly in patients without immunomodulators.

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Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease

Cited by 55 publications

References 41 publications

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease

LRG1: an emerging player in disease pathogenesis

Lymphocyte-to-Monocyte Ratio as a Marker for Endoscopic Activity in Ulcerative Colitis

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