Crohn’s disease (CD) is a complex, chronic, relapsing inflammatory bowel disease (IBD) and typically causes abdominal pain, diarrhoea and sometimes life-threatening complications in patients. This life-long condition significantly reduces patient’s quality of life and has both a large health and economic burden. Genetic, environmental, and immune responses all play a critical role in the pathogenesis of the disease, but it is believed that gut microbiota dysbiosis is the main trigger of CD onset and is linked to the relapsing nature of CD. Many exacerbations of CD have associated blooms in gram negative bacterial species such as Proteobacteria. Additionally, both IgG and IgA titres have been shown to increase in the gut during exacerbations.
Antibody usually protects against bacterial disease, however we have identified a specific antibody towards gram negative bacteria that actually protects these strains from immune killing. This ‘cloaking antibody’ (cAb) is specific for the O-antigen of lipopolysaccharide, and when in high titres prevents complement-mediated killing of the bacteria. Presence of these antibodies has been associated with worse outcomes in respiratory diseases.
To determine whether cAbs exist in patients with CD, we investigated 78 serum samples from patients in the ‘post-operative CD endoscopic recurrence (POCER)’ study. To do this, we extracted LPS from six representative gram negative microbiota-associated bacteria. The titre of IgG and IgA against these extracted LPS samples was determined via ELISA. Up to 40% of the patients displayed high titres of anti-LPS IgG to at least one of the extracts examined. We demonstrated that these antibodies could inhibit normal serum-mediated killing of these bacterial strains. Patients at with high titres of anti-LPS IgG at baseline associated with worse baseline endoscopic scores. These antibodies may be a potential biomarker for worse outcomes in CD.