Background: Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies (pANCA). α-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti–α-enolase antibodies in IBD and related disorders.
Methods: We used a classic proteomic approach with extracts from granulocytes and pANCA-positive ulcerative colitis (UC) sera to confirm α-enolase as a target antigen. By means of Western blot analysis, we screened a cohort of 525 subjects for the presence of anti–α-enolase antibodies. We performed GeneArray experiments on RNA extracted from colonic mucosal biopsies from 35 IBD and 6 control patients.
Results: We detected anti–α-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 α-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–α-enolase antibodies. Preabsorption with α-enolase did not eliminate the pANCA pattern on indirect immunofluorescence.
Conclusions: Anti–α-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–α-enolase antibodies are of limited diagnostic value for the diagnosis of IBD.
IBD patients show strong seroreactivity toward enzymes involved in the glycolysis. IBD patients also have increased colonic mRNA expression of glycolytic enzymes, which is triggered by hypoxia through the transcription factor HIF-1.
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