Monoclonal antibody 197 (anti-FcγRI) infusion in a patient with immune thrombocytopenia purpura (ITP) results in down-modulation of FcγRI on circulating monocytes

Authors


Dr Solveig G. Ericson Robert C. Byrd Health Sciences Center of West Virginia University, Bone Marrow Transplantation Program, Mary Babb Randolph Cancer Center, Section of Hematology/Oncology, P.O. Box 9162, Morgantown, WV 26506-9162, U.S.A.

Abstract

A 44-year-old woman with refractory immune thrombocytopenia purpura was treated with the murine monoclonal antibody 197 in a phase I trial. In vitro studies have demonstrated that the monoclonal antibody 197 (subclass IgG2a) binds to two distinct epitopes of FcγRI, with the constant domain binding to the Fc-binding portion of the FcγRI and the variable domain binding to a different epitope, resulting in crosslinking and modulation of this receptor. The monoclonal antibody 197 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 with transient facial flushing, and wheal-and-flare rash during the first infusion, which resolved with a slower infusion rate and the administration of diphenhydramine and acetaminophen. Although a marked clinical improvement did occur with resolution of oral ecchymoses and epistaxis after the first mAb infusion, the initial platelet count of 6×109 l did not change appreciably over the 5 d course of monoclonal antibody treatment. Binding of fluorescein-labelled monoclonal antibody 197 to peripheral monocytes showed a rapid and persistently decreased mean fluorescence intensity, indicating binding of administered 197 to the monocytes in vivo. Indirect staining for FcγRI using fluorescein-labelled goat anti-mouse immunoglobulin was also decreased, suggesting modulation of the receptor. The patient experienced monocytopenia which persisted throughout the 5 d of monoclonal antibody 197 therapy, but reversed following institution of intravenous IgG. These data indicate that intravenous monoclonal antibody 197 induces specific down-modulation of FcγRI expression on monocytes.

Ancillary