Drug-induced neutropenia associated with anti-neutrophil cytoplasmic antibodies (ANCA): possible involvement of complement in granulocyte cytotoxicity.
Although antineutrophil antibodies are thought to be involved in drug-induced neutropenia, neither the precise mechanisms nor the particular antigens on the neutrophil surface have yet been clarified. Recently, we examined a patient with Graves' disease who developed antineutrophil cytoplasmic antibodies (ANCA) after propylthiouracil treatment and exhibited neutropenia. Because several target antigens of ANCA are expressed on the surface of neutrophils, it was suggested that ANCA might contribute to neutropenia. The patient's serum bound specifically to neutrophils and HL-60 cells differentiated into granulocytes, and lysed the HL-60 cells via a complement-mediated mechanism. Furthermore, two representative ANCA antigens, proteinase 3 and myeloperoxidase, significantly inhibited both the binding and cytotoxicity of the serum. Finally, tumour necrosis factor-alpha, which is known to up-regulate cell surface expression of several ANCA antigens, enhanced both the binding and cytotoxicity of the serum. These findings suggest that ANCA induced by propylthiouracil contributed to leucopenia through a complement-mediated mechanism.
Akamizu
T
T
Department of Medicine and Clinical Science, Kyoto Universoty Graduate School of Medicine, Japan. akataka@kuhp.kyoto-u.ac.jp
Ozaki
S
S
Hiratani
H
H
Uesugi
H
H
Sobajima
J
J
Hataya
Y
Y
Kanamoto
N
N
Saijo
M
M
Hattori
Y
Y
Moriyama
K
K
Ohmori
K
K
Nakao
K
K
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D006111:Graves Disease / Q000188:drug therapy; D018922:HL-60 Cells; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000276:immunology*; D011441:Propylthiouracil / Q000009:adverse effects* / Q000627:therapeutic use
D019268:Antibodies, Antineutrophil Cytoplasmic; D013956:Antithyroid Agents; D011441:Propylthiouracil