iTRAQ-based proteomic identification of leucine-rich  -2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases

Serada, Satoshi; Fujimoto, Minoru; Ogata, Atsushi; Terabe, Fumitaka; Hirano, Tôru; Iijima, Hideki; Shinzaki, Shinichiro; Nishikawa, Teppei; Ohkawara, Tomoharu; Iwahori, Kota; Ohguro, Nobuyuki; Kishimoto, Tadamitsu; Naka, Tetsuji

doi:10.1136/ard.2009.118919

Cited by 180 publications

(191 citation statements)

References 13 publications

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“…Although LRG is able to identify HF in this study, it must be acknowledged that LRG levels are also increased in other diseases. 25,29 This is a limitation that may preclude the use of LRG in the general population as a single marker indicator of HF. Given the difficulties in predicting and diagnosing LVDD and DHF, we suggest that LRG may prove useful in a clinical setting as part of a multimarker approach in combination with routine clinical assessment.…”

Section: Limitationsmentioning

confidence: 99%

Proteomic Analysis of Coronary Sinus Serum Reveals Leucine-Rich α2-Glycoprotein as a Novel Biomarker of Ventricular Dysfunction and Heart Failure

Watson

Ledwidge

Phelan

et al. 2011

Circ: Heart Failure

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Background-Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF. Methods and Results-Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich ␣2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (PՅ0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-␣ (Pϭ0.009) and interleukin-6 (Pϭ0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-␤R1 (PϽ0.001) and ␣-smooth muscle actin (Pϭ0.025) expression. Conclusions-LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, ␤-blocker therapy, and BNP. (Circ Heart Fail. 2011;4:188-197.)Key Words: heart failure Ⅲ hypertension Ⅲ natriuretic peptides Ⅲ leucine-rich ␣2-glycoprotein A lthough therapies for heart failure (HF) have improved, it is clear that effective prevention strategies will have the most important impact on the concerning epidemiology of this syndrome. In this regard, it is essential to complement effective risk factor control with the earliest possible identification of those at risk for progressive ventricular dysfunction and HF. Hypertensive heart disease (HHD) is a welldescribed example of progressive ventricular dysfunction. Currently, it is not known why a certain proportion of patients with hypertension develop diastolic dysfunction (DD) and others do not. Furthermore, the early diagnosis of the transition to HF is critical and can be clinically challenging. A better understanding of the pathophysiological signals at play may allow for more precise diagnostic tests to define the onset of HF. This natural history is not simply explained by the degree of blood pressure control and probably involves complex disease mechanisms still not fully understood. The ability to identify which asymptom...

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Section: Limitationsmentioning

confidence: 99%

Proteomic Analysis of Coronary Sinus Serum Reveals Leucine-Rich α2-Glycoprotein as a Novel Biomarker of Ventricular Dysfunction and Heart Failure

Watson

Ledwidge

Phelan

et al. 2011

Circ: Heart Failure

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“…Serum leucin rich-α2-glycoprotein concentrations were significantly elevated in RA patients as compared to healthy controls and decreased after anti-tumour necrosis factor therapy. Furthermore, serum leucin rich-α2-glycoprotein concentrations correlated with disease activity in RA (Serada, Fujimoto et al 2010). …”

Section: Apps During Ra Disease Stagesmentioning

confidence: 97%

Acute Phase Proteins in Prototype Rheumatic Inflammatory Diseases

Lakota¹,

Frank²,

Buzan³

et al. 2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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“…LRG is an (almost equal to) 50 kDa glycoprotein and contains repetitive sequences with a leucinerich motif [76]. It has been reported to be a novel biomarker in autoimmune disease [77]. Serum LRG concentrations were significantly elevated (14.24 ± 8.08 lg/ ml) in active UC patients compared with in patients in remission (5.34 ± 2.60 lg/ml) (P \ 0.0001) and healthy controls (3.07 ± 1.42 lg/ml) (P \ 0.0001) and also correlated well with disease activity (colitis activity index [CAI]).…”

Section: 227mentioning

confidence: 99%

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

Jiang

2015

Mol Diagn Ther

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Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally invasive tests for IBD diagnosis and/or prognosis as well as assessment of disease activity and response to therapy. Here, we update the current status of IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA [miRNA]) biomarkers. As an update, the classical serological biomarkers, including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan antibodies, are discussed only briefly. Emphasis in this article is given to those that have been recently identified or extensively characterized, as well as to the clinical utilities of biomarkers, with special attention to prediction of disease complication and activity assessment, mucosal healing, and response to therapies. In particular, we discuss the utilities of blood-based biomarkers predicting therapeutic response to anti-tumor necrosis factor (TNF)-α, such as anti-anti-TNFα antibodies or anti-drug antibodies (ADA) and trough level of anti-TNFα. Fecal biomarkers, which have recently attracted substantial attention, are also discussed extensively, including the well-characterized calprotectin and lactoferrin, as well as the recently characterized M2-PK, CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the discovery of a number of rare yet disease-defining IBD-susceptible genes, particularly those involved in very early onset IBD, providing rare yet extremely useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we briefly summarize the discovery, characterization, and potential implications of miRNA as potential IBD biomarkers.

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iTRAQ-based proteomic identification of leucine-rich -2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases

Abstract: LRG represents a novel serum biomarker for monitoring disease activity during therapy in autoimmune patients, particularly useful in patients with active disease but normal CRP levels.

Cited by 180 publications

References 13 publications

Proteomic Analysis of Coronary Sinus Serum Reveals Leucine-Rich α2-Glycoprotein as a Novel Biomarker of Ventricular Dysfunction and Heart Failure

Proteomic Analysis of Coronary Sinus Serum Reveals Leucine-Rich α2-Glycoprotein as a Novel Biomarker of Ventricular Dysfunction and Heart Failure

Acute Phase Proteins in Prototype Rheumatic Inflammatory Diseases

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

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