MONOCLONAL-ANTIBODY-197 (ANTI-FC-GAMMA-RI) INFUSION IN A PATIENT WITHIMMUNE THROMBOCYTOPENIA PURPURA (ITP) RESULTS IN DOWN-MODULATION OF FC-GAMMA-RI ON CIRCULATING MONOCYTES

A 44-year-old woman with refractory immune thrombocytopenia purpura wa s treated with the murine monoclonal antibody 197 in a phase I trial, In vitro studies hare demonstrated that the monoclonal antibody 197 (s ubclass IgG2a) binds to two distinct epitopes of Fc gamma RI, with the constant domain binding to the Fc-binding portion of the Fc gamma RI and the variable domain binding to a different epitope, resulting in c rosslinking and modulation of this receptor. The monoclonal antibody 1 97 was administered on days 1, 3 and 5 at doses of 0.25 mg/kg, 0.35 mg /kg and 0.45 mg/kg, respectively, The infusions were well tolerated wi th transient facial flushing, and wheal-and-flare rash during the firs t infusion, which resolved with a slower infusion rate and the adminis tration of diphenhydramine and acetaminophen, Although a marked clinic al improvement did occur with resolution of oral ecchymoses and epista xis after the first mAb infusion, the initial platelet count of 6 x 10 (9)/l did not change appreciably over the 5 d course of monoclonal ant ibody treatment, Binding of fluorescein-labelled monoclonal antibody 1 97 to peripheral monocytes showed a rapid and persistently decreased m ean fluorescence intensity, indicating binding of administered 197 to the monocytes in vivo. Indirect staining for Fc gamma RI using fluores cein-labelled goat anti-mouse immunoglobulin was also decreased, sugge sting modulation of the receptor. The patient experienced monocytopeni a which persisted throughout the 5 d of monoclonal antibody 197 therap y, but re reversed following institution of intravenous IgG, These dat a indicate that intravenous monoclonal antibody 197 induces specific d own-modulation of Fc gamma RI expression on monocytes.