Roozendaal C, Horst G, Pogány K, van Milligen de Wit A W, Kleibeuker J H, Haagsma E B, Limburg P C, Kallenberg C G
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Adv Exp Med Biol. 1998;443:313-9. doi: 10.1007/978-1-4757-9068-9_39.
Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes. Antibodies with specificity for proteinase 3 and myeloperoxidase are seromarkers for systemic vasculitides. ANCA with specificity for lactoferrin were described in patients with several idiopathic inflammatory diseases, such as the inflammatory bowel diseases and rheumatoid arthritis. However, the clinical significance of anti-lactoferrin autoantibodies is still unclear. In this study, we determined the clinical significance of anti-lactoferrin autoantibodies in sera from large groups of patients with ulcerative colitis (UC), Crohn's disease (CD), and primary sclerosing cholangitis (PSC). Antibodies to human lactoferrin were detected by ELISA and by immunoblotting, using an extract of sonicated neutrophils as antigen source. Autoantibodies to lactoferrin were found in 29% of patients with UC, 13% of patients with CD, and 22% of patients with PSC. In inflammatory bowel diseases, the presence of anti-lactoferrin antibodies was not related to treatment, disease activity, duration of disease, or disease extent. In PSC, the presence of autoantibodies to lactoferrin did not correlate with duration of disease or the presence of cirrhosis. However, patients with PSC and coexistent UC had significantly more frequently antibodies to lactoferrin than PSC patients without IBD. In conclusion, autoantibodies to lactoferrin are a common feature of inflammatory bowel diseases and PSC. However, the clinical significance of those autoantibodies is limited as they lack sensitivity and specificity for those disorders. Future research should address the pathophysiological role of anti-lactoferrin ANCA and the influence of anti-lactoferrin ANCA binding on the functional properties of the lactoferrin molecule.
抗中性粒细胞胞浆抗体（ANCA）是针对中性粒细胞胞浆成分的自身抗体。对蛋白酶3和髓过氧化物酶具有特异性的抗体是系统性血管炎的血清标志物。在几种特发性炎症性疾病患者中，如炎症性肠病和类风湿关节炎，发现了对乳铁蛋白具有特异性的ANCA。然而，抗乳铁蛋白自身抗体的临床意义仍不清楚。在本研究中，我们确定了抗乳铁蛋白自身抗体在大量溃疡性结肠炎（UC）、克罗恩病（CD）和原发性硬化性胆管炎（PSC）患者血清中的临床意义。使用超声处理的中性粒细胞提取物作为抗原来源，通过酶联免疫吸附测定（ELISA）和免疫印迹法检测人乳铁蛋白抗体。在29%的UC患者、13%的CD患者和22%的PSC患者中发现了抗乳铁蛋白自身抗体。在炎症性肠病中，抗乳铁蛋白抗体的存在与治疗、疾病活动度、病程或疾病范围无关。在PSC中，抗乳铁蛋白自身抗体的存在与病程或肝硬化的存在无关。然而，与无炎症性肠病的PSC患者相比，合并UC的PSC患者抗乳铁蛋白抗体的出现频率显著更高。总之，抗乳铁蛋白自身抗体是炎症性肠病和PSC的常见特征。然而，这些自身抗体的临床意义有限，因为它们对这些疾病缺乏敏感性和特异性。未来的研究应探讨抗乳铁蛋白ANCA的病理生理作用以及抗乳铁蛋白ANCA结合对乳铁蛋白分子功能特性的影响。
