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Defective microbial sensing and clearance in perianal Crohn’s disease: a role for complement factor B
  1. Arya Ghate1,
  2. Holm H. Uhlig1,2,3
  1. 1 Translational Gastroenterology Unit, Oxford University, Oxford, UK
  2. 2 Department of Paediatrics, University of Oxford, Oxford, UK
  3. 3 Oxford Biomedical Research Centre (BRC), University of Oxford, Oxford, UK
  1. Correspondence to Professor Holm H. Uhlig, Translational Gastroenterology Unit, Oxford University, Oxford OX4 9DU, UK; holm.uhlig{at}

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Fistulising perianal disease is one of the common presentations in Crohn’s disease (CD).1 Between 12% and 41% of patients with CD develop perianal complications of fistulising disease or abscesses.2 Whereas disease susceptibility in complex and multifactorial CD has been associated with over hundred genetic loci allowing insight into the pathophysiology, the genetic basis and functional mechanisms of disease subphenotypes such as fistulising perianal disease are less well understood and better mechanistic and therapeutic insights are needed.3

Under homeostatic conditions, tissue resident intestinal macrophages with high phagocytic activity ingest and eliminate translocating bacteria in the intestine without eliciting an inflammatory immune response.4 In inflammatory bowel disease (IBD), multiple factors including intestinal dysbiosis and possibly damaged epithelial barrier due to ulceration and inflammatory conditions can cause a significantly higher influx of translocating and potentially invading bacteria. To prevent systemic spreading of bacteria and to compartmentalise bacteria if needed, there exist a number of mechanisms of pathogen recognition including antibody-mediated recognition and complement activation, as well as monocyte and neutrophil accumulation, phagocytosis and intracellular clearance. Cellular response mechanisms also include granuloma formation and fibroblast repair mechanisms, all aimed to reduce bacterial spreading. Perianal fistulising disease and abscess formation is a consequence of incomplete control of invading bacteria and defective repair. Inflammatory T helper (Th)1/Th17 cells, macrophages producing tumour necrosis factor (TNF) and metalloproteinases as well as fibroblasts producing transforming growth factor-β (TGF-β) and interleukin-13 (IL-13) participate in the …

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  • Contributors AG and HU contributed equally.

  • Funding HU has received research support or consultancy fees from UCB Pharma, Janssen, Eli Lilly, MiroBio, Celgene and AbbVie. AG is supported by an Oxford Cartography programme fellowship of Janssen.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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