Autoantibody to c-Mpl (thrombopoietin receptor) in systemic lupus erythematosus: relationship to thrombocytopenia with megakaryocytic hypoplasia.
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.


CONCLUSIONS
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.
Kuwana
Masataka
M
Keio University School of Medicine, Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp
Okazaki
Yuka
Y
Kajihara
Mikio
M
Kaburaki
Junichi
J
Miyazaki
Hiroshi
H
Kawakami
Yutaka
Y
Ikeda
Yasuo
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001854:Bone Marrow Cells / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology*; D008297:Male; D008533:Megakaryocytes / Q000473:pathology* / Q000502:physiology; D008875:Middle Aged; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000209:etiology / Q000276:immunology*; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human