Decreased serum group‐specific component protein levels and complexes with actin in fulminant hepatic necrosis

Monomeric G‐actin has recently been shown to form high‐affinity complexes with group‐specific component protein (Gc), and this process might be expected to occur in vivo when hepatocyte necrosis with release of actin takes place. We therefore measured serum Gc levels and searched for evidence of actin‐containing complexes of Gc in 147 sera from 21 normal subjects and 126 patients with acute and chronic liver diseases. Sera were examined for Gc concentration using an ELISA with purified Gc as standard. Gc levels were greatly diminished (<10 mg per dl) in 5 of 37 patients with acute hepatitis and 1 of 3 patients with subacute hepatic necrosis, and the mean values for these groups overall as well as those for chronic active hepatitis patients were significantly less than that observed in the normal controls (mean, 35.5 mg per dl). No significant alteration in Gc level was observed in the chronic disease categories studied. In contrast, Gc concentrations < 10 mg per dl were found in 12 of 14 patients with fulminant hepatic necrosis, and the mean for this group (9.7) was significantly reduced (p < 0.001). Sequential studies in 12 patients with acute hepatitis of moderate to marked severity but without a fulminant phase showed significant diminutions in initial Gc levels when these were compared with Gc levels obtained during recovery. Using analytical isoclectric focusing with print immunofixation, variable amounts of Gc:G‐actin complexes could be demonstrated in virtually all sera examined, but the proportion of total Gc present as complex with G‐actin appeared greater in fulminant hepatic necrosis sera. The marked reduction of serum Gc levels in fulminant hepatic necrosis is likely due in part to decreased hepatic synthesis of Gc; however, the increase in Gc:G‐actin complexes may also affect Gc levels. These findings support the hypothesis that Gc, in binding to G‐actin, may function to maintain homeostasis in situations of massive actin release.