Farias E Silva Katia, Nanini Hayandra F, Cascabulho Cynthia Machado, Rosas Siane L B, Santana Patricia T, Carneiro Antonio José de V, Anaissie Elias, Nucci Marcio, de Souza Heitor Siffert Pereira
Department of Clinical Medicine, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, Brazil.
Laboratory of Innovations in Therapies, Education and Bioproducts, Instituto Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.
World J Gastroenterol. 2021 Mar 7;27(9):866-885. doi: 10.3748/wjg.v27.i9.866.
1,3-beta-D-glucan (BG) is a ubiquitous cell wall component of gut micro-organisms. We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.
To determine whether the serum BG concentrations correlate with intestinal inflammation.
A prospective observational study was performed in a tertiary referral center, from 2016 to 2019, in which serum BG was determined in 115 patients with Crohn's disease (CD), 51 with ulcerative colitis (UC), and 82 controls using a photometric detection kit. Inflammatory activity was determined by ileocolonoscopy, histopathology, magnetic resonance enterography, and biomarkers, including fecal calprotectin (FC), C-reactive protein, and a panel of cytokines. The ability of BG to detect active inactive disease was assessed using the area under the receiver operating characteristic curve. In subgroup analysis, serial BG was used to assess the response to therapeutic interventions.
The serum BG levels were higher in CD patients than in controls ( = 0.0001). The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients. The area under the curve (AUC) in receiver operating characteristic analysis to predict endoscopic activity was 0.694 [95% confidence interval (CI): 0.60-0.79; = 0.001] in CD, and 0.662 (95%CI: 0.51-0.81; = 0.066) in UC patients. The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860 (95%CI: 0.77-0.95; < 0.001) in CD, and 0.786 (95%CI: 0.57-0.99; = 0.015) in UC patients. The cut-off values of BG for both endoscopic and histologic activity were 60 µg/mL in CD, and 40 µg/mL in UC patients. Performance analysis showed that the results based on BG of 40 and 60 µg/mL were more specific for predicting endoscopic activity (71.8% and 87.2% for CD; and 87.5% and 87.5% for UC, respectively) than FC (53.3% and 66.7% for CD; and 20% and 80% for UC, respectively); and also histologic activity (60.5% and 76.3% for CD; and 90.0% and 95.0% for UC, respectively) than FC (41.7% and 50.0% for CD; and 25% and 50% for UC, respectively). Regarding the clinical, endoscopic, and histologic activities, the BG levels were reduced following therapeutic intervention in patients with CD ( < 0.0001) and UC ( = 0.003). Compared with endoscopic (AUC: 0.693; = 0.002) and histologic (AUC: 0.868; < 0.001) activity, no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography (AUC: 0.576; = 0.192). Positive correlations were detected between BG and IL-17 in the CD (r: 0.737; = 0.001) and the UC group (r: 0.574; = 0.005), and between BG and interferon-gamma in the CD group (r: 0.597; = 0.015).
Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases, particularly in CD.
1,3-β-D-葡聚糖（BG）是肠道微生物普遍存在的细胞壁成分。我们推测BG的血清水平可反映炎症性肠病患者肠道的活动性炎症。
确定血清BG浓度是否与肠道炎症相关。
2016年至2019年在一家三级转诊中心进行了一项前瞻性观察研究，使用光度检测试剂盒对115例克罗恩病（CD）患者、51例溃疡性结肠炎（UC）患者和82例对照者测定血清BG。通过回结肠镜检查、组织病理学、磁共振肠造影以及生物标志物（包括粪便钙卫蛋白（FC）、C反应蛋白和一组细胞因子）来确定炎症活动度。使用受试者工作特征曲线下面积评估BG检测活动期/非活动期疾病的能力。在亚组分析中，使用连续BG评估对治疗干预的反应。
CD患者的血清BG水平高于对照组（P = 0.0001）。BG水平与CD患者的内镜活动度、组织学活动度以及CD和UC患者的内镜与组织学综合活动度平行。受试者工作特征分析中预测内镜活动度的曲线下面积（AUC）在CD患者中为0.694[95%置信区间（CI）：0.60 - 0.79；P = 0.001]，在UC患者中为0.662（95%CI：0.51 - 0.81；P = 0.066）。受试者工作特征分析中预测组织学活动度的AUC在CD患者中为0.860（95%CI：0.77 - 0.95；P < 0.001），在UC患者中为0.786（95%CI：0.57 - 0.99；P = 0.015）。CD患者内镜和组织学活动度的BG临界值均为60μg/mL，UC患者为40μg/mL。性能分析表明，基于40和60μg/mL BG的结果在预测内镜活动度方面比FC更具特异性（CD分别为71.8%和87.2%；UC分别为87.5%和87.5%，而FC在CD中分别为53.3%和66.7%；在UC中分别为20%和80%）；在预测组织学活动度方面也比FC更具特异性（CD分别为60.5%和76.3%；UC分别为90.0%和95.0%，而FC在CD中分别为41.7%和50.0%；在UC中分别为25%和50%）。关于临床、内镜和组织学活动度，CD患者（P < 0.0001）和UC患者（P = 0.003）治疗干预后BG水平降低。与内镜活动度（AUC：0.693；P = 0.002）和组织学活动度（AUC：0.868；P < 0.001）相比，基于磁共振肠造影的血清BG与透壁愈合之间未发现显著相关性（AUC：0.576；P = 0.192）。在CD组（r：0.737；P = 0.001）和UC组（r：0.574；P = 0.005）中检测到BG与IL - 17之间存在正相关，在CD组中BG与干扰素 - γ之间也存在正相关（r：0.597；P = 0.015）。
血清BG可能是检测黏膜炎症和对炎症性肠病进行治疗监测的一种重要的新型非侵入性方法，尤其是在CD中。
