Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Institute of Human Nutrition, Columbia University Medical Center, New York, NY 10032, USA.
Biomolecules. 2023 Oct 16;13(10):1530. doi: 10.3390/biom13101530.
Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate-severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP.
We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 μmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity.
Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m; < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 μmol/L, < 0.001) and at discharge (655 vs. 376 μmol/L, < 0.001). GlycA levels were significantly higher in patients with moderate-severe AP than in those with mild AP at discharge (533 vs. 757 μmol/L, = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 μmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07-32.2; = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48-42.0; = 0.025) than controls.
Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.
急性胰腺炎(AP)是导致胃肠道住院的主要原因,中度至重度 AP 患者的死亡率高达 40%。糖蛋白乙酰化(GlycA)是在炎症期间释放的糖基化急性期蛋白的翻译后修饰的核磁共振信号(NMR)。我们旨在研究 GlycA 作为 AP 炎症生物标志物的作用。
我们前瞻性地招募了 20 名 AP 患者和 22 名健康对照者,并在入院和出院时采集 EDTA 血浆样本。使用 400 MHz Vantera 临床分析仪从这些样本中获取 NMR 光谱,并计算 GlycA 浓度(正常= 400 μmol/L)。NMR 谱中 2.00±0.01 ppm 处的 GlycA NMR 信号源自循环糖蛋白(如 α1-酸性糖蛋白、触珠蛋白、α1-抗胰蛋白酶、α1-抗糜蛋白酶和转铁蛋白)的碳水化合物侧链中的 N-乙酰甲基质子。然后,根据病因和严重程度,将 AP 患者与对照组以及 AP 组内的 GlycA 水平进行比较。
除了 AP 患者的 BMI 高于健康对照组(29.9 与 24.8 kg/m 2 ; <0.001)外,人口统计学比较相似。10 名患者的 AP 为轻度,7 名患者为中度,3 名患者为重度。入院时,AP 患者的 GlycA 水平高于健康对照组(578 与 376 μmol/L, <0.001),出院时也高于健康对照组(655 与 376 μmol/L, <0.001)。与轻度 AP 患者相比,中重度 AP 患者出院时的 GlycA 水平显著升高(533 与 757 μmol/L, =0.023),但入院时则不然。调整 BMI 后,多变量回归表明,GlycA 水平>400 μmol/L 的患者发生任何严重程度的 AP(OR=6.88;95%CI,2.07-32.2; =0.004)和轻度 AP(OR=6.12;95%CI,1.48-42.0; =0.025)的几率显著更高。
我们的初步研究强调了 GlycA 作为 AP 炎症的新型诊断生物标志物的应用。我们的研究表明,与健康对照组相比,住院 AP 患者的 GlycA 水平明显更高。与轻度 AP 患者相比,中重度 AP 患者出院时的 GlycA 水平更高,提示疾病严重的患者存在持续的炎症。