Extracellular vesicle-associated soluble CD163 and CD206 in patients with acute and chronic inflammatory liver disease

<b>Background:</b> Extracellular vesicles (EVs) are implicated in intercellular communication in liver diseases. An EV-associated fraction of the macrophage biomarker soluble CD163, denoted EV-CD163, was recently identified. EV-CD163 may be released during later phases of the inflammatory response as opposed to the acute shedding of CD163 ectodomain (Ecto-CD163). Total sCD163 is a well-described biomarker in liver inflammation, and we investigated the distribution of CD163 fractions along with EV-associated soluble CD206 (EV-CD206) in patients with acute and chronic alcoholic liver inflammation. <b>Methods:</b> Patients with acute alcoholic hepatitis (AH) (<i>n = </i>48) and alcoholic cirrhosis (AC) (<i>n = </i>26) were enrolled. Patients with AH were followed for 30 days after diagnosis. Healthy blood donors (<i>n = </i>30) served as a reference group. Fractions of sCD163 and sCD206 were separated using ExoQuick™ and measured by ELISA. <b>Results:</b> We demonstrated a possible EV-associated fraction of CD206 in plasma, correlating with levels of EV-CD163 (r_s= 0.46, <i>p</i> p p <b>Conclusion:</b> Extracellular vesicles of macrophage origin associated with membrane receptors CD163 and CD206 are present in liver disease. We observed a shift in the distribution towards an increased EV fraction in chronic liver cirrhosis. These data support that Ecto and EV fractions may be markers of different inflammatory processes, possibly resulting from a switch in macrophage phenotype.

背景：细胞外囊泡（Extracellular vesicles, EVs）参与肝脏疾病的细胞间通讯过程。近期研究鉴定出一种与巨噬细胞生物标志物可溶性CD163相关的囊泡组分，命名为EV-CD163。相较于CD163胞外域（Ecto-CD163）的急性脱落，EV-CD163可能在炎症反应的后期阶段被释放。总可溶性CD163（Total sCD163）是肝脏炎症中已被充分表征的生物标志物，本研究针对急性与慢性酒精性肝脏炎症患者，探究了CD163各组分以及囊泡相关可溶性CD206（EV-CD206）的分布情况。
方法：本研究纳入急性酒精性肝炎（AH）患者48例、酒精性肝硬化（AC）患者26例。其中急性酒精性肝炎患者在确诊后接受了为期30天的随访。另招募30名健康献血者作为对照队列。采用ExoQuick™试剂分离sCD163与sCD206的不同组分，并通过酶联免疫吸附试验（ELISA）进行定量检测。
结果：本研究首次在血浆中检测到CD206的EV相关组分，其水平与EV-CD163呈显著正相关（rs=0.46，p<0.001）。相较于健康对照队列，急性酒精性肝炎患者的总sCD163、EV-CD163以及EV-CD206水平均显著升高；而酒精性肝硬化患者则以EV-CD163与EV-CD206占总sCD163的比例升高为主要特征。
结论：源自巨噬细胞、携带有膜受体CD163与CD206的细胞外囊泡存在于肝脏疾病患者体内。本研究观察到，在慢性酒精性肝硬化患者中，囊泡相关组分的占比呈现升高趋势。上述结果提示，CD163的胞外域组分与EV组分或可作为不同炎症进程的标志物，其差异可能源于巨噬细胞表型的转化。