Other
20 Authors
- Ma L,
- Peng J,
- Xu M,
- Tao L,
- Ni H,
- Carrim N,
- Yougbare I,
- Li J,
- Zhai ZM,
- Grozovsky R,
- Zhu G,
- Leytin V,
- Hou M,
- Zhu L,
- Vadasz B,
- Hoffmeister KM,
- Freedman J,
- Zeng Q,
- Ruan M,
- van der Wal DE
| First Author | Li J | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7737 | PubMed ID | 26185093 |
| Mgi Jnum | J:224451 | Mgi Id | MGI:5662309 |
| Doi | 10.1038/ncomms8737 | Citation | Li J, et al. (2015) Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun 6:7737 |
| abstractText | Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests that antibody-mediated platelet destruction occurs in the spleen, via macrophages through Fc-FcgammaR interactions. However, we and others have demonstrated that anti-GPIbalpha (but not GPIIbIIIa)-mediated ITP is often refractory to therapies targeting FcgammaR pathways. Here, we generate mouse anti-mouse monoclonal antibodies (mAbs) that recognize GPIbalpha and GPIIbIIIa of different species. Utilizing these unique mAbs and human ITP plasma, we find that anti-GPIbalpha, but not anti-GPIIbIIIa antibodies, induces Fc-independent platelet activation, sialidase neuraminidase-1 translocation and desialylation. This leads to platelet clearance in the liver via hepatocyte Ashwell-Morell receptors, which is fundamentally different from the classical Fc-FcgammaR-dependent macrophage phagocytosis. Importantly, sialidase inhibitors ameliorate anti-GPIbalpha-mediated thrombocytopenia in mice. These findings shed light on Fc-independent cytopenias, designating desialylation as a potential diagnostic biomarker and therapeutic target in the treatment of refractory ITP. |
