Vermeulen Nathalie, Arijs Ingrid, Joossens Sofie, Vermeire Severine, Clerens Stefan, Van den Bergh Karolien, Michiels Georges, Arckens Lutgarde, Schuit Frans, Van Lommel Leentje, Rutgeerts Paul, Bossuyt Xavier
Department of Internal Medicine, University Hospital Leuven, Leuven, Belgium.
Clin Chem. 2008 Mar;54(3):534-41. doi: 10.1373/clinchem.2007.098368. Epub 2008 Jan 24.
Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (pANCA). alpha-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti-alpha-enolase antibodies in IBD and related disorders.
We used a classic proteomic approach with extracts from granulocytes and pANCA-positive ulcerative colitis (UC) sera to confirm alpha-enolase as a target antigen. By means of Western blot analysis, we screened a cohort of 525 subjects for the presence of anti-alpha-enolase antibodies. We performed GeneArray experiments on RNA extracted from colonic mucosal biopsies from 35 IBD and 6 control patients.
We detected anti-alpha-enolase antibodies 49.0% of patients with UC, 50.0% of patients with Crohn's disease, 30.5% of patients with primary sclerosing cholangitis, 37.8% of patients with autoimmune hepatitis, 34.0% of patients with ANCA-positive vasculitis, 31.0% of non-IBD gastrointestinal controls, and 8.5% of healthy controls. Gene array experiments showed a significant upregulation of alpha-enolase mRNA in colonic mucosal biopsies from patients with IBD, but not from controls. There was no association between the presence of pANCA and anti-alpha-enolase antibodies. Preabsorption with alpha-enolase did not eliminate the pANCA pattern on indirect immunofluorescence.
Anti-alpha-enolase antibodies are present in a substantial proportion of patients with IBD, patients with various inflammatory/autoimmune disorders, and non-IBD gastrointestinal controls. Therefore, anti-alpha-enolase antibodies are of limited diagnostic value for the diagnosis of IBD.
炎症性肠病(IBD)患者携带抗核周型抗中性粒细胞胞浆抗体(pANCA)等自身抗体。α-烯醇化酶已被提出作为IBD中的一种靶抗原。我们评估了IBD及相关疾病中抗α-烯醇化酶抗体的患病率和诊断价值。
我们采用经典蛋白质组学方法,利用粒细胞提取物和pANCA阳性溃疡性结肠炎(UC)血清来确认α-烯醇化酶为靶抗原。通过蛋白质印迹分析,我们筛查了525名受试者队列中抗α-烯醇化酶抗体的存在情况。我们对从35例IBD患者和6例对照患者的结肠黏膜活检组织中提取的RNA进行了基因芯片实验。
我们在49.0%的UC患者、50.0%的克罗恩病患者、30.5%的原发性硬化性胆管炎患者、37.8%的自身免疫性肝炎患者、34.0%的ANCA阳性血管炎患者、31.0%的非IBD胃肠道对照患者以及8.5%的健康对照者中检测到抗α-烯醇化酶抗体。基因芯片实验显示,IBD患者结肠黏膜活检组织中α-烯醇化酶mRNA显著上调,而对照患者中未出现这种情况。pANCA的存在与抗α-烯醇化酶抗体之间无关联。用α-烯醇化酶进行预吸附并未消除间接免疫荧光上的pANCA模式。
抗α-烯醇化酶抗体在相当比例的IBD患者、各种炎症/自身免疫性疾病患者以及非IBD胃肠道对照者中存在。因此,抗α-烯醇化酶抗体对IBD诊断的价值有限。