| First Author | Liu XG | Year | 2016 |
| Journal | Blood | Volume | 128 |
| Issue | 6 | Pages | 852-61 |
| PubMed ID | 27281793 | Mgi Jnum | J:236266 |
| Mgi Id | MGI:5805604 | Doi | 10.1182/blood-2016-01-690727 |
| Citation | Liu XG, et al. (2016) Thrombopoietin receptor agonists shift the balance of Fcgamma receptors toward inhibitory receptor IIb on monocytes in ITP. Blood 128(6):852-61 |
| abstractText | Elevated expression of the activating Fcgamma receptor (FcgammaR) I and FcgammaRIIa together with decreased expression of the inhibitory FcgammaRIIb are involved in the pathogenesis of primary immune thrombocytopenia (ITP). Thrombopoietin receptor agonists (TPO-RAs) have been used clinically for the management of ITP; however, little is known about the effect of TPO-RAs on FcgammaR modulation in ITP. In this prospective study, we measured the alteration in monocyte FcgammaR expression from 21 corticosteroid-resistant/relapsed patients with chronic ITP receiving eltrombopag therapy. Results showed that the mRNA and protein levels of FcgammaRIIb were significantly elevated after 6-week eltrombopag treatment. Concurrently, FcgammaRI and IIa levels decreased remarkably, whereas FcgammaRIII expression did not change. In vitro phagocytosis assays indicated that a shift in the balance of FcgammaR toward inhibitory FcgammaRIIb on monocytes was accompanied with a considerable decrease in monocyte/macrophage phagocytic capacity. The response to eltrombopag therapy in patients with ITP was associated with FcgammaR phenotype and functional changes of monocytes/macrophages. Moreover, the plasma transforming growth factor-beta1 (TGF-beta1) concentrations increased significantly in eltrombopag responders. Modulation of monocyte FcgammaR balance by TPO-RAs was also found in a murine model of ITP established by transferring splenocytes from immunized CD61 knockout mice into CD61(+) severe combined immunodeficient mice. Romiplostim administration in ITP mice significantly upregulated inhibitory FcgammaRII expression and downregulated activating FcgammaRI expression. These findings showed that recovery of platelet counts after TPO-RA treatment in ITP is associated with the restoration of FcgammaR balance toward the inhibitory FcgammaRIIb on monocytes, and suggested that thrombopoietic agents have a profound effect on immune modulation in ITP. This study is registered at ClinicalTrials.gov as #NCT01864512. |
