巨噬细胞活化标志物可溶性 CD163 升高，并与威尔逊病患者的肝病表型相关。
The macrophage activation marker soluble CD163 is elevated and associated with liver disease phenotype in patients with Wilson's disease.
机构信息
Department of Hepatology and Gastroenterology, Aarhus University Hospital, 99 Palle Juul-Jensens Boulevard, DK-8200, Aarhus N, Denmark.
Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany.
出版信息
Orphanet J Rare Dis. 2020 Jul 2;15(1):173. doi: 10.1186/s13023-020-01452-2.
BACKGROUND
Macrophages play a significant role in liver disease development and progression. The macrophage activation marker soluble (s)CD163 is associated with severity and prognosis in a number of different acute and chronic liver diseases but has been only sparsely examined in Wilson's disease (WD). We investigated sCD163 levels in patients with acute and chronic WD and hypothesized associations with liver disease phenotype and biochemical markers of liver injury.
METHODS
We investigated sCD163 in two independent cohorts of WD patients: 28 patients with fulminant WD from the US Acute Liver Failure (ALF) Study Group registry and 147 patients with chronic disease from a German WD registry. We included a control group of 19 healthy individuals. Serum sCD163 levels were measured by ELISA. Liver CD163 expression was determined by immunohistochemistry.
RESULTS
In the ALF cohort, median sCD163 was 10-fold higher than in healthy controls (14.6(2.5-30.9) vs. 1.5(1.0-2.7) mg/L, p < 0.001). In the chronic cohort, median sCD163 was 2.6(0.9-24.9) mg/L. There was no difference in sCD163 according to subgroups based on initial clinical presentation, i.e. asymptomatic, neurologic, hepatic, or mixed. Patients with cirrhosis at the time of diagnosis had higher sCD163 compared with those without cirrhosis (3.0(1.2-24.9) vs. 2.3(0.9-8.0) mg/L, p < 0.001); and both cohorts significantly lower than the ALF patients. Further, sCD163 correlated positively with ALT, AST, GGT and INR (rho = 0.27-0.53); and negatively with albumin (rho = - 0.37), (p ≤ 0.001, all). We observed immunohistochemical CD163 expression in liver tissue from ALF patients.
CONCLUSIONS
Although sCD163 is not specific for WD, it was elevated in WD patients, especially in those with ALF. Further, sCD163 was higher in patients with cirrhosis compared to patients without cirrhosis and associated with biochemical markers of liver injury and hepatocellular function. Thus, macrophage activation is evident in WD and associates with liver disease phenotype and biochemical parameters of liver disease. Our findings suggest that sCD163 may be used as a marker of liver disease severity in WD patients.
背景
巨噬细胞在肝脏疾病的发生和发展中起着重要作用。巨噬细胞激活标志物可溶性（s）CD163 与多种急性和慢性肝病的严重程度和预后相关，但在威尔逊病（WD）中研究甚少。我们研究了急性和慢性 WD 患者的 sCD163 水平，并假设其与肝病表型和肝损伤的生化标志物有关。
方法
我们在两个独立的 WD 患者队列中研究了 sCD163：来自美国急性肝衰竭（ALF）研究组注册的 28 例暴发性 WD 患者和来自德国 WD 注册的 147 例慢性疾病患者。我们纳入了 19 名健康个体作为对照组。通过 ELISA 测定血清 sCD163 水平。通过免疫组织化学测定肝 CD163 表达。
结果
在 ALF 队列中，sCD163 的中位数比健康对照组高 10 倍（14.6(2.5-30.9) vs. 1.5(1.0-2.7) mg/L，p < 0.001）。在慢性队列中，sCD163 的中位数为 2.6(0.9-24.9) mg/L。根据初始临床表现（无症状、神经、肝脏或混合）进行亚组分析时，sCD163 无差异。诊断时患有肝硬化的患者的 sCD163 高于无肝硬化的患者（3.0(1.2-24.9) vs. 2.3(0.9-8.0) mg/L，p < 0.001）；且两个队列均显著低于 ALF 患者。此外，sCD163 与 ALT、AST、GGT 和 INR 呈正相关（rho = 0.27-0.53）；与白蛋白呈负相关（rho = - 0.37），（p ≤ 0.001，均）。我们观察到 ALF 患者肝组织中存在 CD163 的免疫组织化学表达。
结论
尽管 sCD163 不是 WD 的特异性标志物，但在 WD 患者中升高，尤其是在 ALF 患者中升高。此外，肝硬化患者的 sCD163 高于无肝硬化患者，与肝损伤的生化标志物和肝细胞功能相关。因此，巨噬细胞激活在 WD 中很明显，与肝病表型和肝病的生化参数有关。我们的研究结果表明，sCD163 可作为 WD 患者肝病严重程度的标志物。
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