Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Shinzaki, Shinichiro; Matsuoka, Katsuyoshi; Tanaka, Hiroki; Takeshima, Fuminao; Kato, Shingo; Torisu, Takehiro; Ohta, Yuki; Watanabe, Kenji; Nakamura, Shirô; Yoshimura, Naoki; Shiotani, Akiko; Hirai, Fumihito; Hiraoka, Sakiko; Watanabe, Mamoru; Matsuura, Minoru; Nishimoto, Shohei; Mizuno, Shinta; Iijima, Hideki; Takehara, Tetsuo; Naka, Tetsuji; Kanai, Takanori; Matsumoto, Takayuki

doi:10.1007/s00535-021-01793-0

Cited by 40 publications

(44 citation statements)

References 27 publications

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“…Moreover, in some diseases like UC, IL-6 does not play a major role as CRP and SAA often remain at physiological levels [ 30 ]. Thus, the development of novel biomarkers represents an urgent clinical need for the early diagnosis and management of some inflammatory diseases and LRG1, being regulated by multiple pro-inflammatory cytokines, stands as a very promising candidate [ 160 ].…”

Section: Reviewmentioning

confidence: 99%

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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Section: Reviewmentioning

confidence: 99%

LRG1: an emerging player in disease pathogenesis

et al. 2022

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“…Sinzaki et al conducted a prospective study (PLANET study) to investigate the usefulness of LRG as a monitoring biomarker for IBD. Serum LRG levels decreased with improved clinical and endoscopic outcomes during ADA therapy [132]. In a PLANET sub-study, Yanai et al showed that LRG could be a marker for predicting ADA trough levels in ADA-treated patients with CD and UC.…”

Section: Evaluation Of Disease Activity By Lrgmentioning

confidence: 99%

“…Yoshimura et al reported that serum LRG was lower in patients receiving anti-TNF-α agents than those in patients not receiving it [122]. The study by Sinzaki et al suggests that LRG may help monitor disease activity even after anti-TNF-α agents [132]. 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.…”

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

confidence: 99%

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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“…Serum LRG exerted its superiority to mucosal healing in ulcerative colitis rather than C-reactive protein levels (Shinzaki et al, 2017). Serum LRG1 could also act as a useful biomarker to monitoring disease activity of inflammatory bowel disease during anti-TNF treatment (Shinzaki et al, 2021).…”

Section: Part Eight: Lrg1 Involved In Immune Diseasesmentioning

confidence: 99%

Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review

Zou

Chen

et al. 2022

Front. Pharmacol.

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Leucine-rich alpha⁃2 glycoprotein 1 (LRG1) is an important member of the leucine-rich repetitive sequence protein family. LRG1 was mainly involved in normal physiological activities of the nervous system, such as synapse formation, synapse growth, the development of nerve processes, neurotransmitter transfer and release, and cell adhesion molecules or ligand-binding proteins. Also, LRG1 affected the development of respiratory diseases, hematological diseases, endocrine diseases, tumor diseases, eye diseases, cardiovascular diseases, rheumatic immune diseases, infectious diseases, etc. LRG1 was a newly discovered important upstream signaling molecule of transforming growth factor⁃β (TGF⁃β) that affected various pathological processes through the TGF⁃β signaling pathway. However, research on LRG1 and its involvement in the occurrence and development of diseases was still in its infancy and the current studies were mainly focused on proteomic detection and basic animal experimental reports. We could reasonably predict that LRG1 might act as a new direction and strategy for the treatment of many diseases.

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Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Cited by 40 publications

References 27 publications

LRG1: an emerging player in disease pathogenesis

LRG1: an emerging player in disease pathogenesis

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

Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review

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