DOP09 IgG responses to multiple bacterial flagellins identify a subgroup of paediatric therapy-naive Crohn’s disease patients with increased microbiota-specific T-cell reactivity
L. Costes1, I. Tindemans1, M.E. Joosse1, M.A. Aardoom2, M.M.E. Jongsma2, R.H.C. Raatgeep1, D.H. van Haaften1, K.L. Alexander3, L.W. Duck3, A.P. Heikema4, P. Kemos5, J.C. Escher2, F.M. Ruemmele6, N.M. Croft7, C.O. Elson8, L. de Ridder2, J.N. Samsom1
1Laboratory of Pediatrics, Division Gastroenterology and Nutrition, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands, 2Department of Pediatric Gastroenterology, Erasmus University Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands, 3Departments of Immunology, University of Alabama at Birmingham, Birmingham, USA, 4Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands, 5Blizard Institute, Queen Mary University of London, London, UK, 6Service de Gastroentérologie, Sorbonne Paris Cité- APHP, Hôpital Necker Enfants Malades, Université Paris Descartes, Paris, France, 7Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK, 8Department of Medicine, University of Alabama at Birmingham, Birmingham, USA
inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic intestinal disease driven by inflammatory T-cell responses thought to target intestinal bacteria. However, evidence for such microbiota-specific T-cell responses is scarce. Immunoglobulin (Ig) titers to bacterial flagellins are highly elevated in a subgroup of CD patients and associate with a more severe disease course, namely penetrating and stricturing disease. This prompted us to hypothesise that flagellin-specific humoral responses could help uncover the inflammatory T-cell responses underlying disease pathogenesis.
Plasma IgG and IgA reactivity for 12 flagellins from pathogenic and commensal human intestinal bacteria was assessed by antigen microarray in paediatric CD patients (
As previously shown, IgG positivity to at least one flagellin was elevated in virtually all CD and UC patients (73% and 83%, respectively) compared with age-matched healthy controls. Crucially, a third of CD patients showed IgG reactivity to a high diversity of flagellins (8 or more) while UC patients showed IgG reactivity to a maximum of 3 flagellins. Notably, IgG levels specific for the
Our study demonstrates that humoral responses to bacterial flagellins distinguish subgroups of paediatric CD patients. In particular, high diversity in anti-flagellin IgG reactivity is indicative of increased frequencies of anti-flagellin T cells.