Preuss B, Berg C, Altenberend F, Gregor M, Stevanovic S, Klein R
Department of Internal Medicine II, University of Tuebingen, Germany.
Clin Exp Immunol. 2007 Nov;150(2):312-21. doi: 10.1111/j.1365-2249.2007.03482.x. Epub 2007 Aug 17.
It has been shown previously that sera from patients with cholestatic liver diseases react with sulphite oxidase (SO) prepared from chicken liver. In order to analyse this reactivity and the clinical relevance of anti-SO antibodies in more detail, we produced human recombinant SO. Human recombinant SO (60 kDa) was expressed in Escherichia coli and applied to enzyme-linked immunosorbent assay and Western blot. Sera from patients with autoimmune liver disorders [primary biliary cirrhosis (PBC) n = 96; autoimmune hepatitis (AIH) n = 77; primary sclerosing cholangitis (PSC) n = 39], and from patients with other hepatic (n = 154) and non-hepatic chronic inflammatory disorders (n = 113) were investigated. Highest incidence and activities of IgG-anti-SO antibodies were observed in PSC patients. Nine of 16 untreated (56%) and four of 23 PSC patients treated with ursodeoxycholic acid (UDCA) (17%) were positive. Antibody activity decreased significantly during UDCA treatment. Five per cent of PBC and 9% of AIH patients, but also 15% of patients with alcoholic liver disease, were IgG anti-SO-positive. In patients with viral hepatitis and non-hepatic disorders they could be hardly detected. Anti-SO antibodies are further anti-mitochondrial antibodies in chronic liver diseases. They occur predominantly in PSC, and UDCA treatment seams to decrease antibody activity. Whether these antibodies are primary or secondary phenomena and whether they are related to the aetiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.
先前已表明,胆汁淤积性肝病患者的血清与从鸡肝制备的亚硫酸盐氧化酶(SO)发生反应。为了更详细地分析这种反应性以及抗SO抗体的临床相关性,我们制备了人重组SO。人重组SO(60 kDa)在大肠杆菌中表达,并应用于酶联免疫吸附测定和蛋白质印迹。研究了自身免疫性肝病患者[原发性胆汁性肝硬化(PBC)96例;自身免疫性肝炎(AIH)77例;原发性硬化性胆管炎(PSC)39例]以及其他肝病患者(154例)和非肝病慢性炎症性疾病患者(113例)的血清。在PSC患者中观察到IgG抗SO抗体的发生率和活性最高。16例未经治疗的患者中有9例(56%)以及23例接受熊去氧胆酸(UDCA)治疗的PSC患者中有4例(17%)呈阳性。在UDCA治疗期间抗体活性显著降低。5%的PBC患者和9%的AIH患者,还有15%的酒精性肝病患者IgG抗SO呈阳性。在病毒性肝炎和非肝病患者中几乎检测不到。抗SO抗体是慢性肝病中的又一种抗线粒体抗体。它们主要出现在PSC中,并且UDCA治疗似乎会降低抗体活性。这些抗体是原发性还是继发性现象,以及它们是否与病因或发病机制相关,至少在一部分慢性肝病患者中,仍有待评估。