Leucine-rich Alpha-2 Glycoprotein Research Articles

Serum Leucine-Rich Alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Ulceration detected by Capsule Endoscopy

Serum Leucine-Rich Alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Ulceration detected by Capsule Endoscopy

Serum Leucine-Rich Alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Capsule Endoscopy

Serum Leucine-Rich Alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Capsule Endoscopy

Accuracy of Serum Leucine-Rich Alpha-2 Glycoprotein in Evaluating Endoscopic Disease Activity in Crohn's Disease.

Mucosal healing, confirmed by endoscopic evaluation, is the long-term goal of treatment for Crohn's disease (CD). Leucine-rich alpha-2 glycoprotein (LRG) is a new serum biomarker correlated with disease activity in inflammatory bowel disease. However, studies evaluating its relationship with CD, particularly in the context of small intestinal lesions, are scarce. The aim of this study was to investigate the accuracy of LRG in assessing endoscopic activity, especially remission, in patients with CD. Between July 2020 and March 2021, 72 patients with CD who underwent LRG testing and double-balloon endoscopy at the same time were included. Endoscopic activity was evaluated using the applied Simple Endoscopic Score for Crohn's disease, including small intestine lesions. The relationship of LRG with clinical symptoms and endoscopic activity was assessed, and its predictive accuracy was evaluated. Leucine-rich alpha-2 glycoprotein showed a significant positive correlation with endoscopic activity (r = 0.619, P < .001), even in patients with active lesions in the small intestine (r = 0.626, P < .001). Multivariate logistic regression revealed that LRG was the only factor associated with endoscopic remission. An LRG cutoff value of 8.9 μg/mL had a sensitivity of 93.3%; specificity of 83.3%; positive predictive value of 96.6%; negative predictive value of 71.4%; accuracy of 91.7%; and area under the curve of 0.904 for the prediction of endoscopic remission. Leucine-rich alpha-2 glycoprotein can be used in assessing endoscopic activity and is a reliable marker of endoscopic remission in CD patients. It can be an intermediate target in the treatment of CD.

Serum Leucine-Rich alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Capsule Endoscopy

Serum Leucine-Rich alpha-2 Glycoprotein in Quiescent Crohn's Disease as a Potential Surrogate Marker for Small-Bowel Capsule Endoscopy

A Three-Protein Panel to Support the Diagnosis of Sepsis in Children.

Sepsis is a syndrome without a standard validated diagnostic test. Early recognition is crucial. Serum proteome analysis in children with sepsis may identify new biomarkers. This study aimed to find suitable blood biomarkers for an early diagnosis of sepsis. An analytical observational case-control study was carried out in a single center. Children admitted to a Pediatric Intensive Care Unit with clinical diagnosed sepsis were eligible for study. A proteomic analysis conducted by mass spectrometry was performed. Forty patients with sepsis and 24 healthy donors were recruited. Proteomics results revealed 44 proteins differentially expressed between patients and healthy controls. Six proteins were selected to be validated: lactoferrin, serum amyloid-A1 (SAA-1), complement factor B, leucine-rich alpha-2 glycoprotein (LRG1), soluble interleukin-2 alpha chain receptor (sCD25) and soluble haptoglobin–hemoglobin receptor. Our results showed that sCD25, SAA-1, and LRG1 had high levels of specificity and sensitivity, as well as an excellent area under the ROC curve (>0.9). Our study provides a serum proteomic analysis that identifies new diagnostic biomarkers in sepsis. SAA-1, sCD25 and LRG1 were able to separate septic from healthy donor, so they could be used together with other clinical and analytical features to improve sepsis diagnosis in children.

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus.

Coronavirus disease 2019 (COVID-19) raises the issue of how hypoxia destroys normal physiological function and host immunity against pathogens. However, there are few or no comprehensive omics studies on this effect. From an evolutionary perspective, animals living in complex and changeable marine environments might develop signaling pathways to address bacterial threats under hypoxia. In this study, the ancient genomic model animal Takifugu obscurus and widespread Vibrio parahaemolyticus were utilized to study the effect. T. obscurus was challenged by V. parahaemolyticus or (and) exposed to hypoxia. The effects of hypoxia and infection were identified, and a theoretical model of the host critical signaling pathway in response to hypoxia and infection was defined by methods of comparative metabolomics and proteomics on the entire liver. The changing trends of some differential metabolites and proteins under hypoxia, infection or double stressors were consistent. The model includes transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and epidermal growth factor (EGF) signaling pathways, and the consistent changing trends indicated that the host liver tended toward cell proliferation. Hypoxia and infection caused tissue damage and fibrosis in the portal area of the liver, which may be related to TGF-β1 signal transduction. We propose that LRG (leucine-rich alpha-2-glycoprotein) is widely involved in the transition of the TGF-β1/Smad signaling pathway in response to hypoxia and pathogenic infection in vertebrates as a conserved molecule.

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

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.

Leucine-Rich Alpha-2 Glycoprotein in Monitoring Disease Activity and Intestinal Stenosis in Inflammatory Bowel Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 μg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Association of Plasma Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) with All-Cause and Cause-Specific Mortality in Individuals with Type 2 Diabetes.

Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein in the transforming growth factor-beta superfamily. We sought to study whether LRG1 might predict risk for all-cause and cause-specific mortality in individuals with type 2 diabetes. 2012 outpatients with type 2 diabetes were followed for a median of 7.2 years and 188 death events were identified. Association of LRG1 with risk for mortality was assessed by multivariable Cox regression models. Participants with a higher concentration of LRG1 had an increased risk for all-cause mortality [HR (95% CI), 1.76 (1.03-3.01), 1.75 (1.03-2.98), and 4.37 (2.72-7.02) for quartiles 2, 3, and 4, respectively, compared to quartile 1]. The association remained significant after adjustment for known cardio-renal risk factors including estimated glomerular filtration rate and albuminuria [adjusted HR 2.76 (1.66-4.59), quartile 4 versus 1]. As a continuous variable, a 1-SD increment in LRG1 was associated with 1.34 (1.14-1.57)-fold adjusted risk for all-cause mortality. High plasma LRG1 was independently associated with mortality attributable to cardiovascular disease, infection, and renal diseases. Adding LRG1 into a clinical variable-based model improved discrimination (c statistics from 0.828 to 0.842, P = 0.006) and reclassification (net reclassification improvement 0.47, 95% CI 0.28-0.67) for prediction of 5-year all-cause mortality. Plasma LRG1 predicts risk for all-cause mortality and mortality attributable to cardiovascular disease, infection, and renal disease independent of known cardio-renal risk factors. It may be a potential novel biomarker to improve risk stratification in individuals with type 2 diabetes.

Cerebrospinal Fluid Leucine-Rich Alpha-2 Glycoprotein (LRG) Levels in Children with Acute Bacterial Meningitis.

This study evaluated the diagnostic role of cerebrospinal fluid leucine-rich alpha-2 glycoprotein (CSF LRG) concentration in children with acute bacterial meningitis, and its role in differentiation from aseptic meningitis. CSF LRG concentration was measured by ELISA Kit of 50 children with bacterial meningitis, 16 aseptic meningitis, and 20 children with normal CSF; control. CSF LRG was significantly elevated (p < 0.001) in bacterial meningitis with a sensitivity, specificity, PPV, and NPV of 96%, 100%, 100%, and 90.9%, respectively at a cutoff of 110.0ng/mL, based on ROC curve. At the same cutoff value, CSF LRG has sensitivity, specificity, PPV, and NPV of 96%, 75%, 92.3%, and 85.7%, respectively in differentiating bacterial from aseptic meningitis. However, sensitivity, specificity, PPV, and NPV at 139.9ng/mL for differentiating between definite and probable bacterial meningitis were 88%, 75%, 79.1%, and 84.9%, respectively. CSF LRG should be used as a diagnostic biomarker for bacterial meningitis.

Serum exosome-derived biomarkers for the early detection of oral squamous cell carcinoma

Blood exosomes help regulate communication between tumour cells, moderating their behaviour. We sought to determine the protein content in serum exosomes (SEs), to characterise SEs, and to discover novel clinical biomarkers of oral squamous cell carcinoma (OSCC). Differentially expressed proteins (DEPs) of OSCC were identified using proteomics and then analysed using bioinformatics, before validation using ELISA, IHC, and RT-PCR. The influence of SEs on oral cancer cells was detected using CCK-8 and migration assays. Twelve DEPs were found in SEs from OSCC. Four proteins were targeted for further verification. New biomarkers exhibiting high sensitivity and specificity in diagnosing OSCC comprised C-reactive protein (CRP), von willebrand factor (VWF), and leucine-rich alpha-2-glycoprotein (LRG). Combined biomarkers outperformed any single protein. We also demonstrated that tumour-derived exosomes promoted tumour cell migration, but not proliferation and apoptosis. Our study indicates that CRP, VWF, and LRG are potential clinically relevant OSCC biomarkers. OSCC-related SEs may help promote migration of oral cells.

Leucine-Rich Alpha-2 Glycoprotein May Be Predictive of the Adalimumab Trough Level and Antidrug Antibody Development for Patients with Inflammatory Bowel Disease: A Sub-Analysis of the PLANET Study

Introduction: The aim of this study was to examine whether biomarkers are predictive of the adalimumab (ADA) trough level and antidrug antibody development in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Using data obtained in a prospective, multicenter, observational study (PLANET), we assessed serial changes in a novel biomarker – leucine-rich alpha-2 glycoprotein (LRG) – during ADA treatment for patients with active CD and UC. We measured serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCAL) at weeks 0, 12, 24, and 52. The ADA trough level and anti-ADA antibody (AAA) were also measured at weeks 12 and 52. Correlations between the ADA trough level, AAA, and biomarkers were examined. Results: In all, 34 patients with CD and 47 patients with UC were enrolled. The ADA trough level at week 12 or at the time of ADA withdrawal was 8.5 ± 3.9 in the AAA-negative group (n = 70) and 2.9 ± 2.7 μg/mL in the AAA-positive group (n = 8) (p < 0.0001). The ADA trough level at week 12 or at the time of ADA withdrawal was associated with pretreatment LRG (p = 0.0437 and r = −0.23). Conclusion: LRG, rather than CRP or fCAL, may be a marker for predicting the trough level of ADA for patients with CD and UC treated with ADA.

30-OR: Identification of LRG1 as an Insulin Sensitizing Adipokine

Adipocytes play a central role in obesity, type 2 diabetes, and metabolic disease. White adipocytes store excess energy, and brown adipocytes dissipate chemical energy into heat. In addition to these bioenergetics functions, adipocytes also have important endocrine properties. Bioinformatic analyses suggest that adipocytes may secrete over 1,000 unique polypeptides, the vast majority of which remain uncharacterized. We employed bio-orthogonal non-canonical amino acid tagging (BONCAT) along with mass spectrometry to comprehensively characterize the secreted proteome of murine subcutaneous and visceral white adipocytes and interscapular brown adipocytes. We identified more than 700 unique proteins, with approximately 300 showing fat cell type specific enrichment. We here describe a novel role for leucine-rich alpha-2 glycoprotein 1 (LRG1), a secreted protein expressed across all types of adipose tissues. Plasma LRG1 levels were increased in aged and diet-induced obese (DIO) mice. Longitudinal overexpression of LRG1, using an adeno-associated virus (AAV) with tropism for adipose tissue, led to significantly improved glucose and insulin tolerance in DIO mice, despite equivalent body weights. AAV-mediated overexpression of LRG1 in the db/db model of type 2 diabetes resulted in accelerated weight gain due to increased white fat mass, but improved insulin tolerance and a delayed diabetic phenotype. LRG1 overexpressing mice had markedly reduced macrophage accumulation in white adipose tissues, and LRG1 significantly reduced pro-inflammatory gene expression. Taken together, these data suggest LRG1 acts as an insulin sensitizer by promoting healthier lipid storage with reduced inflammation. Disclosure C. J. Choi: None. W. Barr: None. M. Koenen: None. Z. Lin: None. S. Szwed: None. P. Cohen: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-17-ACE-17 to P.C.)

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

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn’s disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

Serum and Urine Biomarker Leucine-Rich Alpha-2 Glycoprotein 1 Differentiates Pediatric Acute Complicated and Uncomplicated Appendicitis.

Purpose: This prospective, single-center cohort study analyzes the potential of inflammatory protein mediator leucine-rich alpha-2 glycoprotein 1 (LRG1) for the early and accurate diagnosis of acute appendicitis (AA), and differentiation of acute complicated (AcA) from uncomplicated appendicitis (AuA). Methods: Participants were divided into the AcA, AuA, and control groups, and their serum (s-LRG1) and urine LRG1 (u-LRG1) levels were assayed preoperatively on the second and fifth postoperative days. Results: 153 patients participated, 97 had AA. Preoperative u-LRG1 with a cut-off value of 0.18 μg/mL generated an area under the receiver operated characteristic (AUC) curve of 0.70 (95% CI 0.62–0.79) for AA versus control (p < 0.001), while the results for AcA versus AuA were not significant (AUC 0.60, 95% CI 0.49–0.71, p = 0.089). The s-LRG1 levels of AA versus the control with a cut-off value of 51.69 μg/mL generated an AUC of 0.94 (95% CI 0.91–0.99, p < 0.001). The cut-off value of s-LRG1 was 84.06 μg/mL for diagnosis of AcA from AuA, and therefore, significant (AUC 0.69, 95% CI 0.59–0.80, p = 0.001). Conclusions: LRG1 exhibited excellent diagnostic performance as an inexpensive, non-invasive, rapid, and accurate biomarker able to reflect the pathogenesis of AA. LRG1 has the potential to replace advanced imaging to diagnose clinically ambiguous AA cases.

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

BackgroundThis multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD).MethodsPatients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC.ResultsA total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426).ConclusionsSerum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Pancreatic Cancer Risk Prediction Model Using a Multi-biomarker Panel

The pancreatic ductal adenocarcinoma (PDAC) has dismal survival rate due to late detection. Thus, many researches have been tried to discover diagnostic biomarkers for early detection of PDAC. Previously, we developed the triple marker panel, including leucine-rich alpha-2 glycoprotein (LRG1), transthyretic (TTR), and CA 19-9, with sensitivity of 82.5%; specificity of 92.1% 1. Now, in this study, using this panel, we were to discover a risk prediction model for pancreatic cancer for early diagnosis with the enzyme-linked immunosorbent assay (ELISA). There were 744 samples assessed with ELISA, including PDACs (n=396) and normal samples (n=348). We proposed a risk prediction model with machine-learning method, logistic regression (LR), and compared it with support vector machine (SVM) and random forest (RF). To commercialize this model, we searched two optimal thresholds to distinguish three risk groups (high, intermediate, and low) that reliably satisfy four measurements, negative predictive value (NPV), positive predictive value (PPV), sensitivity (SEN), and specificity (SPE), simultaneously greater than 0.95%. The Pearson correlation between the triple marker panel examined with ELISA and the individual marker panel examined with ELISA 1 was 0.884. The risk prediction model distinguished pancreatic cancer from normal individuals with AUC 0.935. The thresholds in between low, intermediate and high groups were 0.11 and 0.77, that satisfied NPV 95.15%, PPV 97.55%, SEN 97.55%, and SPE 95.15%.We first validated reproducibility of the performance of the triple marker panel in this study. And our risk prediction model for pancreatic cancer achieved high accuracy prediction, which can be easily used in the clinic.

Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[−] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21–13.7] μg/ml) than in the CAM-f(−) (3.61 [2.71–4.65] μg/ml) or control group (3.39 [2.81–3.93] μg/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.

Leucine-rich alpha-2 glycoprotein (LRG): A novel acute phase protein expressed in Stage 3 Grade C periodontitis before and after periodontal therapy.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel acute phase protein involved in inflammation-associated diseases and that considered to be induced by multiple proinflammatory cytokines. This study aimed to investigate gingival crevicular fluid (GCF) and serum levels of LRG, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in patients with Stage 3 periodontitis before and after non-surgical periodontal treatment. Twenty-five Stage 3 periodontitis and twenty-five periodontally healthy individuals were enrolled in the study. Clinical periodontal measurements were recorded; periodontitis patients received non-surgical periodontal treatment, and GCF and serum samples were obtained at baseline and at 6weeks after treatment. LRG, IL-6 and TNF-α were determined by ELISA. GCF and serum LRG, IL-6 and TNF-α were significantly higher in periodontitis group than healthy controls (P<.001). A significant decrease in GCF and serum LRG, IL-6 and TNF-α was detected after periodontal treatment compared with baseline values of periodontitis patients (P<.001). Our findings revealed that LRG expression was increased in Stage 3 periodontitis both locally and systemically, and non-surgical periodontal therapy was effective in reducing LRG levels in GCF and serum of these patients.