High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcγ receptors on monocytes in patients with primary immune thrombocytopenia

The human Fc gamma receptor (Fc gamma R) system is composed of 2 opposing families, the activating Fc gamma Rs (Fc gamma RI, Fc gamma RIIa, and Fc gamma RIII) and the inhibitory Fc gamma R (Fc gamma RIIb). The disturbed balance of the activating and inhibitory Fc gamma Rs has been implicated in the pathogenesis of many autoimmune diseases. In this study, the expression of Fc gamma Rs on monocytes was determined in 23 patients with primary immune thrombocytopenia (ITP) before and after high-dose dexamethasone (HD-DXM) treatment. The Fc gamma RI expression was significantly higher in ITP patients and decreased after HD-DXM treatment. The ratio of Fc gamma RIIa/IIb mRNA expression on monocytes was significantly higher in untreated patients than in healthy controls. After HD-DXM therapy, the ratio decreased and the increased expression of Fc gamma RIIb mRNA and protein coincided with a remarkable decrease in the expression of Fc gamma RIIa, Fc gamma RI, and monocyte phagocytic capacity. There was no significant difference in Fc gamma RIII expression on monocytes between patients and controls. In vitro cell-culture experiments showed that DXM could induce Fc gamma RIIa and Fc gamma RIIb expression in monocytes from ITP patients, with Fc gamma RIIb at higher amplitudes. These findings suggested that the disturbed Fc gamma R balance might play a role in the pathogenesis of ITP, and that HD-DXM therapy could shift monocyte Fc gamma R balance toward the inhibitory Fc gamma RIIb in patients with ITP. (Blood. 2011; 117(6): 2061-2069)