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

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. Patients with acute alcoholic hepatitis (AH) (48) and alcoholic cirrhosis (AC) (26) were enrolled. Patients with AH were followed for 30 days after diagnosis. Healthy blood donors (30) served as a reference group. Fractions of sCD163 and sCD206 were separated using ExoQuick™ and measured by ELISA. We demonstrated a possible EV-associated fraction of CD206 in plasma, correlating with levels of EV-CD163 (r = 0.46,  < .001). The distribution of biomarker fractions was skewed toward EVs in chronic cirrhosis for both biomarkers (median: 35.8% EV-CD163, 58.8% EV-CD206) as compared to AH patients (median: 26.2% EV-CD163  < .0001, 48.8% EV-CD206,  < .01). In AH patients, total sCD163 and Ecto-CD163 at inclusion were related to survival, whereas EV-CD163 was not. 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.