Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: Relationship to thrombocytopenia with megakaryocytic hypoplasia
Article first published online: 9 AUG 2002
Copyright © 2002 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 46, Issue 8, pages 2148–2159, August 2002
How to Cite
Kuwana, M., Okazaki, Y., Kajihara, M., Kaburaki, J., Miyazaki, H., Kawakami, Y. and Ikeda, Y. (2002), Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: Relationship to thrombocytopenia with megakaryocytic hypoplasia. Arthritis & Rheumatism, 46: 2148–2159. doi: 10.1002/art.10420
- Issue published online: 9 AUG 2002
- Article first published online: 9 AUG 2002
- Manuscript Accepted: 2 APR 2002
- Manuscript Received: 26 NOV 2001
- Keio University Medical Science Fund
- Japanese Ministry of Health and Welfare
- Japanese Ministry of Education, Science, Sports, and Culture
To examine the prevalence, clinical associations, and pathogenic role of autoantibodies to c-Mpl, the thrombopoietin (TPO) receptor, in patients with systemic lupus erythematosus (SLE).
Sera from 69 SLE patients, 84 patients with idiopathic thrombocytopenic purpura (ITP), and 60 healthy individuals were screened for anti–c-Mpl antibodies by enzyme-linked immunosorbent assay using recombinant c-Mpl as an antigen. Clinical findings, autoantibody profiles, and serum TPO levels were compared between SLE patients with and without anti–c-Mpl antibodies. A pathogenic role for the anti–c-Mpl antibody was evaluated by examining its inhibitory effect on TPO-dependent cell proliferation and megakaryocyte colony formation.
Serum anti–c-Mpl antibody was detected in 8 SLE patients (11.6%) and 7 ITP patients (8.3%), but in none of the healthy controls. Anti–c-Mpl antibody was associated with thrombocytopenia (P = 0.0002) and a decrease in bone marrow megakaryocytes (P = 0.02) in SLE patients. Serum TPO levels in thrombocytopenic SLE patients with anti–c-Mpl antibodies were significantly elevated compared with levels in those without the antibodies (P = 0.007). IgG fractions purified from anti–c-Mpl antibody–positive sera bound to c-Mpl expressed on the cell surface and inhibited TPO-dependent cell proliferation and megakaryocyte colony formation.
Autoantibody to c-Mpl is present in a subset of SLE patients with thrombocytopenia and megakaryocytic hypoplasia. It is likely that the impaired thrombopoiesis in these patients is mediated by the anti–c-Mpl antibody, which functionally blocks an interaction between TPO and c-Mpl.