Objective:
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).
Methods:
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.
Results:
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.
Conclusion:
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.