Hydralazine binds covalently to complement component C4

FEBS Letters

Law, Sai-Kit A.²  Sim, Edith¹ 

[1] Wellcome Immunotoxicology Unit, Department of Pharmacology, South Parks Road, Oxford OX1 3QT, England;MRC Immunochemistry Unit, Rex Richards Building, South Parks Road, Oxford OX1 3QU, England

关键词: Drug toxicity Immune complex disease MHC;   

DOI  :  10.1016/0014-5793(85)80631-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Long-term treatment with hydralazine is sometimes associated with deposition of immune complexes and development of systemic lupus erythematosus (SLE) as an adverse side-effect. Hydralazine inhibits the covalent binding reaction of the complement protein C4. We show that when hydralazine inhibits C4, it becomes covalently bound to the polypeptide chain containing the active site thiol ester. C4 is encoded at 2 adjacent polymorphic loci, C4A and C4B, within the major histocompatibility complex. We show that hydralazine binds more efficiently to the C4A than to the C4B gene product and suggest that C4 type may predispose patients to hydralazine-induced SLE.

【 授权许可】

Unknown