Serum Leucine-rich Alpha-2 Glycoprotein Research Articles

P0839 Monitoring disease activity using intestinal ultrasonography in patients with Crohn’s disease treated with risankizumab

Abstract Background Few studies have used intestinal ultrasonography (IUS) to monitor disease activity in patients with Crohn’s disease (CD) treated with risankizumab (RZB). In this study, we investigated the temporal changes in IUS findings among patients with CD who had received RZB. Methods We retrospectively collected data from patients with CD who received their first dose of RZB between January 2023 and February 2024, with baseline and subsequent IUS evaluations at our clinic. Patients with a colostomy were excluded from the study. IUS was performed using the Aplio a550 at baseline and at 4, 8, 12, 20, and 28 weeks for each intestinal segment (small bowel, ascending, transverse, descending, and sigmoid colons). Findings for each segment were analyzed using IUS indicators, including bowel wall thickness (BWT) and bowel wall stratification (BWS), while blood flow signals in the intestinal wall were assessed using superb microvascular imaging (SMI). Active BWT was defined by a value of ≥3 mm for the small bowel or ≥4 mm for the colon. The segment with the thickest BWT was considered the representative finding for each patient. BWS were categorized into preserved or loss of BWS. SMI signals were evaluated using our own simplified grading system based on the Limberg score: grade 0, no vascularization; grade 1, short stretches of vascularity as spots; grade 2, longer stretches of vascularity; or grade 3, longer stretches of vascularity reaching the mesentery 1). Changes in BWT, BWT reduction rates, loss of BWS, and SMI grade from weeks 0 to 28 were evaluated. Results This study included 28 patients (median age, 31.0 years; median disease duration, 6.0 years), 8 of whom were female. The median BWT at baseline was 5.3 mm. Preservation and loss of BWS were observed in 7 and 21 patients, respectively, and SMI grades of 0, 1, 2, and 3 were observed in 1, 11, 11, and 5 patients, respectively. The BWT and BWT reduction rates at 4, 8, 12, 20, and 28 weeks were 5.2 mm, 5.2 mm, 4.8 mm, 4.6 mm, and 4.5 mm and −1.9%, −2.8%, −10.1%, −12.2%, and −17.4%, respectively. Both values decreased significantly after 8 weeks. Loss of BWS was observed in 78.6%, 75.0%, 71.4%, 60.7%, and 60.7% of patients at 4, 8, 12, 20, and 28 weeks, respectively, and SMI grade 0 was observed in 17.9%, 17.9%, 25.0%, 39.3%, and 50.0% of patients at 4, 8, 12, 20, and 28 weeks, respectively, with a significant increase after 12 weeks. Conclusion IUS revealed that BWT changed significantly in patients with CD 8 weeks after treatment with RZB, while blood flow changed significantly 12 weeks post-treatment. Loss of BWS responded poorly even after 28 weeks of treatment. Time-dependent changes should be considered when monitoring disease activity in CD treated with RZB using IUS. References 1)Nasuno M, Shimazaki H, Nojima M, Hamada T, Sugiyama K, Miyakawa M, Tanaka H. Serum leucine-rich alpha-2 glycoprotein levels for predicting active ultrasonographic findings in intestinal lesions of patients with Crohn’s disease in clinical remission. Medicine (Baltimore). 2023;102(32):e34628. doi: 10.1097/MD.0000000000034628.

P0424 Utility of superb microvascular imaging for predicting terminal ileal lesion activity in Crohn’s disease

Abstract Background Superb microvascular imaging (SMI) is rarely used in intestinal ultrasonography (IUS) to evaluate Crohn’s disease (CD) activity. This study investigated SMI findings that can predict small or large ulcers in the terminal ileum and compared them with endoscopic findings of patients with CD. Methods Data were retrospectively collected from patients with CD who underwent IUS between September 2020 and April 2024 at our clinic and ileocolonoscopy to evaluate the terminal ileum within 3 months before or after IUS. Patients with a history of small bowel resection were excluded from the study. Based on the endoscopic findings, the lesions in the terminal ileum were classified as follows: no, aphthous (<5 mm), small (5–20 mm) and large (>20 mm) ulcers. IUS was performed using Aplio a550. SMI signals were evaluated using our simplified grading system based on the Limberg score: grade 0, no vascularisation; grade 1, short stretches of vascularity as spots; grade 2, longer stretches of vascularity or grade 3, longer stretches of vascularity reaching the mesentery 1). The modified Limberg score using SMI (mLS-SMI) was applied, with the substituted SMI grade, and the proportion of patients with endoscopic findings indicating small or large ulcers in each mLS-SMI and SMI grades was evaluated. The sensitivity and specificity of the respective mLS-SMI and SMI grades for predicting endoscopic findings of small or large ulcers were also assessed. Results This study included 204 patients (median age, 29.0 years; median disease duration, 5.2 years), 50 of whom were female. The endoscopic findings were as follows: no (n = 96), aphthous (n = 68), small (n = 25) and large (n = 15) ulcers. In total, 164, 14, 13, 11 and 5 patients presented with mLS-SMI grades 0, 1, 2, 3 and 4, respectively. Moreover, 157, 27, 12 and 8 patients exhibited SMI grades 0, 1, 2 and 3, respectively. Further, 10%, 29%, 69%, 64% and 80% of patients with mLS-SMI grades 0, 1, 2, 3 and 4, respectively, and 8%, 52%, 67% and 75% of those with SMI grades 0, 1, 2 and 3, respectively, presented with endoscopic findings indicating small or large ulcers. The sensitivity and specificity of mLS-SMI grades ≥1, ≥2, ≥3 and ≥4 for predicting small or large ulcers were 60% and 88%, 50% and 95%, 28% and 97% and 10% and 99%, respectively. The sensitivity and specificity of SMI grades ≥1, ≥2 and ≥3 for predicting small or large ulcers were 70% and 88%, 35% and 96%, and 15% and 99%, respectively. Conclusion The proportion of patients with endoscopic small or large ulcers increased with mLS-SMI and SMI grades. The sensitivity and specificity of SMI grade ≥1 were comparable to mLS-SMI grade ≥1, suggesting that SMI grade alone may suffice for evaluation. References 1)Nasuno M, Shimazaki H, Nojima M, Hamada T, Sugiyama K, Miyakawa M, Tanaka H. Serum leucine-rich alpha-2 glycoprotein levels for predicting active ultrasonographic findings in intestinal lesions of patients with Crohn’s disease in clinical remission. Medicine (Baltimore). 2023;102(32):e34628. doi: 10.1097/MD.0000000000034628.

Serum Leucine-Rich Alpha-2 Glycoprotein 1 Levels in Patients with Lipodystrophy Syndromes.

Serum concentrations of leucine-rich alpha-2 glycoprotein 1 (LRG1) are elevated in several cardio-metabolic and inflammatory diseases. LRG1 also plays an important role in the development of hepatic steatosis and insulin resistance. In lipodystrophies (LDs), severe cardio-metabolic complications can be observed. The dysregulation of several adipokines plays a significant role in the clinical manifestation of this syndrome. To date, there have been no studies of LRG1 levels in non-HIV-LD patients. We performed a cross-sectional analysis of LRG1 serum levels in 60 patients with non-HIV-associated LD and in 60 age-, sex-, and BMI-matched healthy controls. Furthermore, we investigated the gene expression of Lrg1 in a mouse model of generalised LD. No significant difference was found in the median concentration of LRG1 serum levels between LD patients (18.2 ng/L; interquartile range 8.3 ng/L) and healthy controls (17.8 ng/L; interquartile range 11.0 ng/L). LRG1 serum concentrations correlated positively with CRP serum levels (p < 0.001). Lrg1 mRNA expression was downregulated in the adipose tissue, whereas in the liver, no difference in Lrg1 expression between LD and wild-type mice was detected. In summary, circulating levels of LRG1 are associated with low-grade inflammation but cannot distinguish between patients with LD and controls.

Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn's disease during biological remission.

Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn's disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD. This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD. Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=-0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification. LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.

Leucine-rich alpha-2 glycoprotein is useful in predicting clinical relapse in patients with Crohn's disease during biological remission.

Serum leucine-rich alpha-2 glycoprotein (LRG) is a potential biomarker of Crohn's disease (CD). This study aimed to evaluate the usefulness of LRG in predicting clinical relapse in patients in remission with CD. This retrospective observational study assessed the relationships among patient-reported outcome (PRO2), LRG, and other blood markers. The influence of LRG on clinical relapse was assessed in patients in remission with CD. Data of 94 patients tested for LRG between January 2021 and May 2023 were collected. LRG level did not correlate with PRO2 score (ρ = 0.06); however, it strongly correlated with C-reactive protein (CRP) level (r=0.79) and serum albumin level (r=-0.70). Among 69 patients in clinical remission, relapse occurred in 22 patients (31.9%). In the context of predicting relapse, LRG showed the highest area under the curve, followed by CRP level, platelet count, and albumin level. Multivariate analysis revealed that only LRG (P= 0.02) was an independent factor for predicting clinical remission. The cumulative non-relapse rate was significantly higher in patients with LRG < 13.8 μg/mL than in patients in remission with LRG ≥ 13.8 μg/mL and normal CRP level (P= 0.002) or normal albumin level (P= 0.001). Cumulative non-relapse rate was also higher in patients with LRG < 13.8 μg/mL compared to those with LRG ≥ 13.8 μg/mL in patients with L3 or B2+B3 of Montreal calcification. LRG is useful in predicting clinical relapse in patients with CD during biological remission. LRG is a useful biomarker for predicting prognosis, even in patients with intestinal stenosis, or previous/present fistulas.

Efficacy of serum leucine-rich alpha-2 glycoprotein in predicting findings of Crohn's disease small bowel lesion in capsule endoscopy.

Small bowel capsule endoscopy (SBCE) is an evaluation method for small bowel (SB) lesions in Crohn's disease (CD). However, the relationship between SBCE findings and the serological biomarker leucine-rich alpha-2 glycoprotein (LRG) remains unclear. We aimed to establish appropriate cutoff values of LRG to predict the presence of SB lesions in CD through SBCE. Patients with CD with SB lesions who had undergone SBCE and LRG measurements 1 month before and after the SBCE were included. The LRG values for ulcers ≥0.5 cm and other inflammatory lesions noted in SBCE were determined using the Youden Index, and the sensitivity and specificity were calculated. Additionally, the correlation between the SBCE scores (CD Activity in Capsule Endoscopy) and LRG values was evaluated. Forty patients without active colorectal lesions were included in the study. When the cutoff value of LRG for SB ulcers ≥ 0.5 cm was set at 14 μg/mL, the sensitivity was 92.3%, specificity was 81.5%, positive predictive value (PPV) was 70.6%, and negative predictive value (NPV) was 95.7%. In contrast, an LRG cutoff value of 12 μg/mL without inflammatory findings had a sensitivity of 91.7%, specificity of 82.1%, PPV of 68.8%, and NPV of 95.8%. CD Activity in Capsule Endoscopy correlated well with LRG values (Spearman's rank correlation coefficient ρ = 0.681, P< 0.001). An LRG cutoff value of 14 μg/mL may be useful in predicting the presence of SB ulcers ≥ 0.5 cm, and an LRG cutoff value of 12 μg/mL may be useful in predicting the absence of SB inflammatory findings.

USEFULLNESS OF SERUM LEUCINE-RICH ALPHA2-GLYCOPROTEIN AND FECAL CALPROTECTIN ASSURROGATE MARKERS IN ULCERATIVE COLITIS

Abstract BACKGROUND AND AIM Serum Leucine-rich alpha-2 glycoprotein (LRG) was identified as a novel biomarker for rheumatoid arthritis and IBD by using a proteomics approach. Several studies have suggested that serum LRG levels and fecal calprotectin (fCal) were correlated with clinical activities in patients with ulcerative colitis (UC). We compared utility of these biomarkers for monitoring disease activity in UC. METHODS A single-center observational study was conducted at Kyushu University Hospital. A total of 101 patients who underwent colonoscopy during the period from February to December 2021 were enrolled. The associations between endoscopic and histological activity and biomarkers were investigated. Endoscopic activity was defined as Mayo endoscopic score (MES) of 1 or less for mucosal healing and 0 for complete mucosal healing. For histological activity (n=90), Geboes score of 2 or less was defined as histological remission. RESULTS Subjects ranged in age from 16 to 80 years (35 males and 66 females). There were 63 cases of total colitistype, 32 cases of left-sided colitis type, and 6 cases of proctitis type. The MES at enrollment were as follows: MES 0 in 41 cases, MES 1 in 33 cases, MES 2 in 19 cases, and MES 3 in 8 cases. In comparison between the mucosal healing and non-mucosal healing groups, LRG was significantly lower in the mucosal healing group (p&amp;lt;0.0001). The correlation coefficient of LRG with MES was r=0.614 (p&amp;lt;0.0001), which was higher than that of fCal, r=0.414 (p&amp;lt;0.0001). In ROC analysis with mucosal healing as the outcome, the AUC and cut-off value of LRG were 0.781 and 17.9 μg/ml, respectively, and for fCal were 0.850 and 396 μg/g, respectively. In the ROC analysis with complete mucosal healing as the outcome, the AUC for LRG was 0.690, which was lower than the AUC of 0.846 for fCal . When compared by histological remission, LRG was lower in the histological remission group (p&amp;lt;0.001). In the ROC analysis with histological remission as the outcome, the AUC for LRG was 0.722 (cutoff value 14.2 μg/ml) and for fCal was 0.837 (cutoff value 119 μg/g). CONCLUSION Both LRG and fCal are valuable biomarkers reflecting disease activity in UC.

P660 Serum Leucine-rich Alpha-2 Glycoprotein Can be a Biomarker for Selecting Anti-Cytokine Biologics in Patients with Inflammatory Bowel Disease: A Multicentre Prospective Cohort Study

Abstract Background Serum leucine-rich alpha-2 glycoprotein (LRG) is a biomarker reflecting endoscopic activity in patients with inflammatory bowel disease (IBD). However, it remains unclear whether serum LRG can predict the effectiveness of anti-cytokine biologics (biologics) in patients with IBD. This study aimed to evaluate whether serum LRG could predict the effectiveness and serum trough concentrations of biologics in patients with IBD. Methods This was a multicentre prospective cohort study including patients with IBD (including ulcerative colitis [UC] or Crohn’s disease [CD]) who received the biologics [ustekinumab (UST), anti-tumor necrosis factor (anti-TNF)] from January 2019 to March 2023 at 15 hospitals participating in the Osaka Gut Forum. The effectiveness of biologics was evaluated by clinical remission (CR) at week 8. We defined CR as a partial Mayo score of 2 or lower, with each subscore of 0 or 1 for UC and a CD activity index of &amp;lt; 150 for CD. Factors associated with CR at week 8 such as backgrounds, disease activities and concomitant medications at week 0 were analyzed by Cox proportional hazards model. For each biologic, we compared the effectiveness of biologics in the high LRG group with that in the low LRG group divided by the median serum LRG levels at week 0 (cut-off = 18.2 μg/mL). Results A total of 184 patients with IBD (UC, 80; CD, 104) were enrolled (UST/ anti-TNF, 119/ 65; biologic exposure, 31.5%; median disease duration, 6 years [Interquartile range (IQR) 1-14]). Median serum LRG levels at week 0 and serum C-reactive protein levels at week 0 were 18.2 μg/mL [IQR 12.5-28.1] and 0.19 mg/dL [IQR 0.03-0.77], respectively. At week 0, 63 (34.2%) and 64 (34.8%) patients concomitantly received corticosteroids and immunomodulators, respectively. In 184 patients with IBD, multivariate analysis revealed that serum LRG level at week 0 &amp;lt; 18.2 μg/mL was extracted as a significant factor for CR at week 8 (Odds ratio: OR 2.70, 95% confidence interval: CI 1.22-5.96). In patients who received UST, the proportion of CR at week 8 in the low-LRG group (76.9%) was significantly higher than that in the high-LRG group (59.3%, P = 0.038). In patients who received anti-TNF, however, the proportion of CR in the low-LRG group (84.6%) was not differ from that in the high-LRG group (82.1%, P = 0.781). Median serum trough concentrations of UST at week 8 in the low-LRG group (10.9 μg/mL, IQR 6.7-13.4) was significantly higher than that in the high-LRG group (5.3 μg/mL, IQR 2.4-8.3, P &amp;lt; 0.001). Conclusion Serum LRG could predict the effectiveness and serum trough concentrations of UST and be a biomarker for selecting biologics in patients with IBD.

Significance of Serum Leucine-rich Alpha-2 Glycoprotein as a Diagnostic Marker in Pediatric Inflammatory Bowel Disease.

Serum leucine-rich alpha-2 glycoprotein (LRG) has been utilized for adult inflammatory bowel disease (IBD); however, its efficacy in pediatric IBD remains unknown. The aim of this study was to compare the diagnostic accuracy of serum LRG for pediatric IBD with that of current inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This retrospective case-control study included pediatric patients, aged <16 years, who underwent colonoscopy and/or esophagogastroduodenoscopy between April 2017 and March 2022. All eligible patients were divided into two groups: patients with IBD, diagnosed with ulcerative colitis and Crohn's disease, and non-IBD controls. The optimal cut-off value of serum LRG for IBD diagnosis was determined from receiver operating characteristic analysis, and diagnostic accuracy of serum LRG was compared to serum ESR and CRP. A total of 53 patients (24 with IBD and 29 non-IBD controls) met the inclusion criteria. The cut-off value of serum LRG for IBD diagnosis was determined to be 19.5 μg/ml. At this cut-off value, serum LRG had a positive predictive value (PPV) of 0.80 and negative predictive value (NPV) of 0.88. In contrast, PPV and NPV were 0.78 and 0.70 for serum ESR and 0.82 and 0.72 for serum CRP, respectively. Serum LRG can be a potential diagnostic marker for pediatric IBD, with higher diagnostic accuracy than that of the conventional serum markers ESR and CRP.

Study the evaluation of serum Leucine-Rich Alpha-2 Glycoprotein as a biomarker for ulcerative colitis activity in ulcerative colitis patients

Study the evaluation of serum Leucine-Rich Alpha-2 Glycoprotein as a biomarker for ulcerative colitis activity in ulcerative colitis patients

Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis.

In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

Combined serum albumin, fecal immunochemical test, and leucine-rich alpha-2 glycoprotein levels for predicting prognosis in remitting patients with ulcerative colitis

This study investigated the usefulness of serum leucine-rich alpha-2 glycoprotein (LRG) and fecal immunochemical tests (FIT) for predicting relapse in patients with ulcerative colitis (UC). Data of 194 patients tested for LRG between January 2020 and June 2022 were retrospectively collected and clinical characteristics were recorded. LRG was strongly correlated with CRP levels and it had a moderately negative correlation with albumin levels, whereas FIT was not significantly correlated with either CRP or albumin levels. Furthermore, the median serum albumin and FIT were significantly different between patients with or without clinical relapse; while the LRG level was not associated with clinical relapse. Although LRG is not an independent factor for predicting clinical relapse, the cumulative remission rate was significantly higher in patients with higher albumin than in those with lower albumin. Furthermore, the combination of FIT and albumin was useful for predicting for relapse, patients with higher FIT and lower albumin tended to have higher relapse rates than those with both lower FIT and albumin and those with lower FIT and higher albumin. Our study indicated that serum albumin level is useful for predicting relapse, even in remitting outpatients. Although LRG is not an independent factor for predicting clinical relapse, it is useful for identifying patients that are likely to relapse when combined serum albumin or FIT results.

Serum leucine-rich alpha-2 glycoprotein levels for predicting active ultrasonographic findings in intestinal lesions of patients with Crohn's disease in clinical remission.

This study aimed to investigate the cutoff value of leucine-rich alpha-2 glycoprotein (LRG) in predicting active intestinal ultrasonography (IUS) findings in patients with Crohn's disease (CD) in clinical remission. Data were retrospectively collected from patients with CD evaluated using LRG and undergoing IUS from September 2020 to August 2022. Patients with a Harvey-Bradshaw Index of ≤4 were included and those who underwent intestinal resection were excluded. Bowel wall thickness and stratification and blood flow signal using superb microvascular imaging (SMI) were used to assess ultrasonography findings. SMI signals were categorized into 4 grades following the Limberg score. Receiver operating characteristic curves were constructed and the area under the curve was calculated to determine the LRG cutoff values for predicting active IUS findings and were compared with those of C-reactive protein. This study included 213 patients. The LRG cutoff values to predict active bowel wall thickness, loss of bowel wall stratification, and SMI of ≥1, ≥2, and 3 were 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, 14.6 μg/mL, and 16.9 μg/mL, respectively, with significantly higher areas under the curve in SMI of ≥1 and 3 than in C-reactive protein. The best LRG cutoff value for predicting active IUS findings was 14.6 μg/mL in patients with CD in clinical remission, suggesting that LRG is better than C-reactive protein for detecting active IUS findings in CD.

Systematic Review and Meta-Analysis of the Use of Serum Leucine-Rich Alpha-2 Glycoprotein to Assess Crohn's Disease Activity.

Although fecal calprotectin is the most widely used biomarker for assessing Crohn's disease activity, serum leucine-rich alpha-2 glycoprotein has recently attracted attention, especially in Japan. Here we performed a systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein to obtain evidence for its accuracy in assessing Crohn's disease activity. On February 1, 2023, we performed searches of PubMed, Web of Science, and CENTRAL. The Prospero number is CRD42023396034. The primary outcomes were the sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein for assessing Crohn's disease activity. We used a bivariate generalized linear mixed model, assuming a binomial distribution at the test level and a bivariate normal distribution at the between-test level. We selected 9 studies involving 797 individuals in our systematic review. Regarding the primary outcomes, the synthesized sensitivity and specificity of serum leucine-rich alpha-2 glycoprotein were 77.0% (95% confidence interval, 67.8% to 84.2%) and 81.1% (95% confidence interval, 72.6% to 87.4%), respectively. The area under the curve was 0.86, and the partial area under the curve was 0.78. Regarding between-study heterogeneity, both the I2 value by Zhou and Dendukuri approach and the I2 value by Holling sample size-adjusted approaches were 0%. Our systematic review and meta-analysis of serum leucine-rich alpha-2 glycoprotein demonstrated its accuracy in assessing Crohn's disease activity. Further studies are needed to demonstrate its clinical utility and clinical validity.

Serum leucine-rich alpha-2 glycoprotein and calprotectin in children with inflammatory bowel disease: A multicenter study in Japan.

Serum leucine-rich alpha-2 glycoprotein (LRG) and calprotectin have been studied as disease activity markers in adults with inflammatory bowel disease (IBD). We evaluated them in pediatric IBD patients. Subjects under 17years old undergoing care at 11 Japanese pediatric centers were retrospectively assigned to 3 groups representing Crohn's disease (CD), ulcerative colitis (UC), and normal controls (NC) with irritable bowel syndrome or no illness. Serum LRG and calprotectin were measured using commercial enzyme-linked immunosorbent assay kits. We enrolled 173 subjects, including 74 with CD, 77 with UC, and 22 NC. Serum LRG concentrations in active CD (median, 200μg/mL) were significantly greater than in remission (81μg/mL; P<0.001) or NC (69μg/mL; P<0.001). Serum calprotectin concentrations in active CD (2941ng/mL) also were significantly greater than in remission (962ng/mL; P<0.05) or NC (872ng/mL; P<0.05). Serum LRG concentrations in active UC (134μg/mL) were significantly greater than in remission (65μg/mL; P<0.01) but not significantly greater than in NC (69μg/mL); serum calprotectin concentrations in active UC (1058ng/mL) were not significantly different from those in remission (671ng/mL) or NC (872ng/mL). In receiver operating characteristic analyses of LRG, calprotectin, C-reactive protein, and erythrocyte sedimentation rate for ability to distinguish active IBD from remission, CD and UC showed areas under receiver operating characteristic curves for LRG (0.77 and 0.70, respectively), exceeding those for calprotectin, C-reactive protein, or erythrocyte sedimentation rate. In pediatric IBD, serum LRG may better reflect disease activity than serum calprotectin, particularly in CD.

Usefulness of Serum Leucine-Rich Alpha-2 Glycoprotein as a Surrogate Marker of Small Bowel Mucosal Injury in Crohn’s Disease

Introduction: Although the importance of mucosal healing has been suggested in Crohn’s disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel. Methods: We retrospectively analyzed the clinical data of 30 patients with Crohn’s disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn’s Disease Activity Index [CECDAI], and Crohn’s Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE. Results: LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) (p < 0.05, Spearman’s rank correlation coefficient). The degree of correlation was greater for LRG than for CRP. Conclusions: LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.

Optimal Use of Serum Leucine-Rich Alpha-2 Glycoprotein as a Biomarker for Small Bowel Lesions of Crohn’s Disease

Introduction: A large proportion of small bowel lesions in Crohn’s disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD. Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded. Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61–0.87), 0.69 (0.52–0.81), and 0.77 (0.59–0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP <3 mg/L (26, MH; 32, small bowel inflammation) was 0.68 (0.50–0.81) and 0.74 (0.54–0.84), respectively. The cut-off of 16 μg/mL of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00, while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/mL. Conclusion: LRG can accurately detect and/or exclude the small bowel lesions with two cut-off values.

Serum leucine-rich alpha-2 glycoprotein levels in rheumatoid arthritis and spondyloarthritis: A promising biomarker

Background: In the early stages of the disease, some of the signs and symptoms of joint inflammation in rheumatoid arthritis (RA) may resemble that of spondyloarthritis (SpA). An examination that can help distinguish RA and SpA is warranted. One such examination is the measurement of serum leucine-rich alpha-2 glycoprotein (LRG) levels. This study aimed to measure serum LRG levels in RA and SpA patients and determine the role of LRG in the diagnosis of RA and SpA. Methods: This is a cross-sectional study consisting of 26 RA subjects and 26 SpA subjects. The SpA subjects were further grouped into ankylosing spondylitis (AS), psoriatic arthritis (PsA), and peripheral SpA. Measurement of serum LRG levels were conducted using ELISA. Difference between LRG levels of the two groups were compared using the Mann-Whitney test. Results: LRG levels were elevated in 76.9% and 84.6% of subjects with RA and SpA, respectively. The median LRG levels were higher in RA subjects (77.03 (27.16–107.73)) than SpA (68.67 (33.15–115.18)). There was no significant difference in LRG levels in RA and SpA subjects (p = .442). The RA and PsA group were predominated by diseases of moderate activity, 88.5% and 58.3%, respectively. In comparison, AS was dominated by high disease activity (85.7%). The highest median LRG levels in AR and SpA subjects were in new-onset patients (82.21 vs. 72.25 µg/dL). Conclusions: There was no significant difference in LRG levels between RA and SpA subjects. The role of LRG in the diagnosis of RA and SpA remains to be determined in future studies.

Serum leucine-rich alpha-2 glycoprotein as a predictive factor of endoscopic remission in Crohn's disease.

The usefulness of fecal calprotectin (FC) and serum leucine-rich alpha-2 glycoprotein (LRG) assessing the activity of Crohn's disease (CD) remains to be fully demonstrated in Asia. The present study aimed to elucidate whether FC and LRG could predict endoscopic remission (ER) in Japanese patients with CD. Between October 2018 and July 2021, we prospectively observed treatment courses of CD patients treated with biologic agents. The optimal cutoff values of Crohn's Disease Activity Index (CDAI), serum C-reactive protein (CRP), serum albumin (Alb), FC, and LRG levels for predicting ER at week 52 were calculated using receiver operating characteristic (ROC) curves. We also analyzed the correlations between the achievement of clinical remission (CR) or biomarker remission (BR) at week 12/24/52 and ER at week 52. Among 53 patients who completed 52weeks of observation, 20 (37.7%) achieved ER at week 52. Using the calculated cutoff values, patients who achieved CR (CDAI≤112) or BR (CRP≤0.42mg/dL, Alb≥3.8g/dL, FC≤287μg/g, or LRG≤13.6μg/mL) at week 12/24/52 had a higher ER rate at week 52. FC-BR at week 12/24 showed low sensitivity (0.58/0.60)but high specificity (0.78/0.74)for predicting ER; LRG-BR at week 12/24 also showed low sensitivity (0.68/0.74) but high specificity (0.87/0.78). However, FC-BR and LRG-BR at week 52 had improved sensitivity (0.80/0.84) while specificity remained (0.79/0.85). From the early phase of biologic treatment, both FC and LRG had high specificity for predicting ER at week 52. LRG showed higher sensitivity than FC.

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

Background: Small bowel (SB) lesions in quiescent Crohn’s disease (CD) are sometimes not identified by clinical activity or existing markers. We investigated the usefulness of a novel biomarker, leucine-rich α2-glycoprotein (LRG), for screening for the presence of SB ulcerative lesions detected by small-bowel capsule endoscopy (SBCE). Methods: We examined patients with a Crohn’s Disease Activity Index (CDAI) value < 150 and a C-reactive protein (CRP) value < 0.5 mg/dL with SB or SB colonic CD. The presence of small-bowel ulcerative lesions (≥0.5 cm) was grouped by SBCE results, and we then compared the groups’ LRG value to establish a cutoff value for screening for the presence of lesions. Results: In 40 patients with CD, the LRG values differed significantly between the patients with and without SB ulcerative lesions (Ul + 14.1 (2.1–16.5) μg/mL vs. Ul − 12.3 (9.3–13.5) μg/mL; p = 0.0105). The respective cutoff LRG values for the presence of SB ulcerative lesions was 14 μg/mL (areas under the ROC curve 0.77), with sensitivity 63.6%, specificity 82.8%, positive predictive values 58.3%, negative predictive values 85.7%, and accuracy 78%. Conclusion: These results indicate that LRG may be useful in predicting the presence of SB inflammation associated in patients with CD with CRP < 0.5 mg/dL and CDAI < 150, and in selecting patients for SBCE.