Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2024

Do anti-LPS antibodies to patient microbiota associate with worse outcomes in Crohn's disease?  (104575)

Wenkang Feng 1 , Lauren Scooth 1 , Jingjie Teh 1 , Naiqi Yao 1 , Amy Hamilton 2 , Michael Kamm 3 , Mark Morrison 1 , Timothy Wells 1
  1. Frazer Institute, University of Queensland, Brisbane, Queenslnad, Australia
  2. Department of Medicine, The University of Melbourne, Melborne, Victoria, Australia
  3. Department of Gastroenterology, St Vincent’s Hospital, Melborne, Victoria, Australia

Crohn’s disease (CD) is a complex, chronic, relapsing inflammatory bowel disease (IBD) and typically causes abdominal pain, diarrhea and sometimes life-threatening complications in patients.  Genetic, environmental, and immune factors contribute to its pathogenesis. Gut microbiota dysbiosis is believed to be a primary trigger linked to its relapsing nature. Many exacerbations of CD have associated blooms in gram-negative bacterial species such as Proteobacteria. Additionally, both high IgG and high C5a (an inflammatory byproduct of the complement pathway) in the gut have been associated with the severity of CD. Antibodies usually promote killing of gram-negative bacteria by activation of the complement cascade leading to lysis. We however have shown that IgG2 or IgA specific for the LPS of various gram negatives, although activating the complement cascade, actually protects bacteria from complement-mediated lysis. These ‘cloaking antibodies’ are associated with worse outcomes in respiratory diseases but their role in CD is unknown.

 

To investigate the role of cloaking antibodies in CD, we investigated 78 serum samples from patients in the ‘post-operative CD endoscopic recurrence (POCER)’ study. We extracted LPS from six representative gram-negative microbiota-associated bacteria including Escherichia fergusonii, Morganella morganii, Klebsiella pneumonia, Bacteroide vulgatus, Veillonella ratti and Proteus mirabilis. The titre of IgG and IgA against these LPS samples was determined via ELISA. We also measured the C5a level of patient sera measured before and 180 mins after challenge with gram-negative strains. Up to 40% of the patients displayed high titres of anti-LPS IgG to at least one of the six species. We found these patient antibodies could inhibit healthy control serum-killing of these bacterial strains. Importantly, high titres of anti-LPS IgG at baseline were associated with worse endoscopic scores after six months. In preliminary results, we found c5a level significantly increased after patient sera contact with gram-negative strains compared to healthy control serum. These antibodies may be a potential biomarker for worse outcomes in CD.

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