P178 Validation of the clinical utility of IFI16-based markers in IBD
Caneparo V.1,2, Pastorelli L.3,4, Vanni E.5,6, Roggenbuck D.7,8, Boldorini R.9, Astegiano M.6, Vecchi M.3,4, Landolfo S.1, Gariglio M.2, De Andrea M.*1,2
1University of Turin, Medical School, Department of Public Health and Pediatric Sciences, Viral Pathogenesis Unit, Turin, Italy 2University of Piemonte Orientale, Department of Translational Medicine, Virology Unit, Novara, Italy 3IRCCS Policlinico San Donato, Gastroenterology and Digestive Endoscopy Unit, San Donato Milanese, Milan, Italy 4University of Milan, Department of Biomedical Sciences for Health, Milan, Italy 5University of Turin, Department of Medical Sciences, Gastroenterology Unit, Turin, Italy 6AOU Città della Salute e della Scienza - Molinette Hospital, Gastroenterology and Hepatology Unit, Turin, Italy 7Brandenburg University of Technology Cottbus-Senftenberg, Institute of Biotechnology, Senftenberg, Germany 8GA Generic Assays GmbH, Dahlewitz, Germany 9University of Piemonte Orientale, Department of Health Sciences, Pathology Unit, Novara, Italy
Although the exact cause of IBD remains unknown, available evidence suggests that an abnormal immune response against the intestinal microorganisms is responsible for the disease in genetically susceptible individuals. Recent advances in immunology and genetics have clarified that the innate immune response is as important as adaptive immunity in inducing gut inflammation in IBD patients. Significant alterations in the expression and function of pattern recognition receptors (PRRs), including the IFI16 protein, were indeed described in colonic mucosal biopsies from active ulcerative colitis (UC) patients versus healthy controls (Vanhove et al., Inflamm Bowel Dis 2015). We have recently extended these analyses to Crohn's disease (CD) patients (Caneparo et al., Inflamm Bowel Dis 2016). Furthermore, because we have previously demonstrated that IFI16 protein is a target for autoantibodies, this study aimed to evaluate its specific seroresponse in a large and heterogeneous cohort of patients with IBD.
To date, we have measured anti-IFI16 antibodies (IgG and IgA subtypes) in the sera of 157 patients with IBD: 113 patients with CD and 44 patients with UC, prospectively harvested before and after therapy. The patient antibody statuses were qualitatively and quantitatively associated with disease phenotype and response to therapy, and compared to those for anti-GP2 antibodies.
In a cohort of patients undergoing Infliximab (IFX) treatment, we have recently observed significantly higher titers of anti-IFI16 IgG in both CD and UC patients compared with healthy controls. Anti-IFI16 IgA titers were also present in patients with CD. Finally, significant changes in anti-IFI16 IgG subtype titers after IFX therapy were demonstrated in patients with CD, which correlate with clinical remission. In the present study, we have extended this analysis to a larger IBD cohort including patients with therapy other than IFX. The results substantiate that anti-IFI16 autoantibody titers are significantly higher in IBD patients than in controls. Moreover, IgG and IgA titers correlate with different specific clinical features in CD patients.
Our recent results have highlighted the importance of IFI16 in IBD pathogenesis showing that its