Mulder A H, Horst G, Haagsma E B, Limburg P C, Kleibeuker J H, Kallenberg C G
Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
Hepatology. 1993 Mar;17(3):411-7.
To evaluate the diagnostic significance of neutrophil cytoplasmic antibodies in chronic liver diseases, we assessed the prevalence of neutrophil cytoplasmic antibodies in autoimmune liver diseases, in particular in primary sclerosing cholangitis, autoimmune chronic active hepatitis and primary biliary cirrhosis, and we also determined the specificity of perinuclear-pattern neutrophil cytoplasmic antibodies for these autoimmune liver diseases by testing sera from patients with nonautoimmune chronic liver diseases. Neutrophil cytoplasmic antibodies were detected in 79% of sera from patients with primary sclerosing cholangitis (n = 24), in 88% of sera from patients with autoimmune chronic active hepatitis (n = 24) and in 28% of sera from patients with primary biliary cirrhosis (n = 25). The presence of neutrophil cytoplasmic antibodies in these diseases correlated significantly (p < 0.008) with the presence of cirrhosis. Neutrophil cytoplasmic antibodies were not detected in nonautoimmune liver diseases. All neutrophil cytoplasmic antibody-positive sera produced a perinuclear fluorescence pattern on ethanol-fixed granulocytes. On neutrophils fixed with paraformaldehyde, a granular cytoplasmic immunofluorescence pattern was observed, demonstrating the cytoplasmic nature of the antigen or antigens involved. Further characterization studies showed that neutrophil cytoplasmic antibodies in autoimmune liver diseases are not directed against myeloperoxidase, proteinase 3 or elastase, the neutrophil cytoplasmic antibody specificities associated with necrotizing vasculitis, glomerulonephritis or both. On Western blots neutrophil cytoplasmic antibodies in autoimmune liver diseases showed reactivity with either lactoferrin, a 67/66-kD protein combination or a 40-kD polypeptide. Reactivity with either of these proteins was observed in sera from patients with primary sclerosing cholangitis (38%), autoimmune chronic active hepatitis (17%) and primary biliary cirrhosis (20%).(ABSTRACT TRUNCATED AT 250 WORDS)
为评估中性粒细胞胞浆抗体在慢性肝病中的诊断意义，我们检测了自身免疫性肝病，尤其是原发性硬化性胆管炎、自身免疫性慢性活动性肝炎和原发性胆汁性肝硬化患者中中性粒细胞胞浆抗体的流行情况，并通过检测非自身免疫性慢性肝病患者的血清来确定核周型中性粒细胞胞浆抗体对这些自身免疫性肝病的特异性。原发性硬化性胆管炎患者（n = 24）血清中79%检测到中性粒细胞胞浆抗体，自身免疫性慢性活动性肝炎患者（n = 24）血清中88%检测到，原发性胆汁性肝硬化患者（n = 25）血清中28%检测到。这些疾病中中性粒细胞胞浆抗体的存在与肝硬化的存在显著相关（p < 0.008）。非自身免疫性肝病中未检测到中性粒细胞胞浆抗体。所有中性粒细胞胞浆抗体阳性血清在乙醇固定的粒细胞上产生核周荧光模式。在用多聚甲醛固定的中性粒细胞上，观察到颗粒状胞浆免疫荧光模式，证明了所涉及抗原的胞浆性质。进一步的特性研究表明，自身免疫性肝病中的中性粒细胞胞浆抗体并非针对髓过氧化物酶、蛋白酶3或弹性蛋白酶，这些是与坏死性血管炎、肾小球肾炎或两者相关的中性粒细胞胞浆抗体特异性。在免疫印迹法中，自身免疫性肝病中的中性粒细胞胞浆抗体与乳铁蛋白、一种67/66-kD蛋白组合或一种40-kD多肽发生反应。原发性硬化性胆管炎患者（38%）、自身免疫性慢性活动性肝炎患者（17%）和原发性胆汁性肝硬化患者（20%）的血清中观察到与这些蛋白之一的反应性。（摘要截断于250字）
