One major form of inflammatory bowel disease -- Crohn's disease -- affects five million people in the world. The disease affects the gastrointestinal tract, abdominal pain, diarrhea, fatigue, weight loss and malnutrition. But in some people, the disease also harm the musculoskeletal system, leading to a painful disease known as spondyloarthritis that affects the joints and the entheses.
A study led by Randy Longman at Weill Cornell Medicine now provides insight into why this occurs. The researchers found that a strain of E. coli may be responsible for spondyloarthritis in Crohn's disease patients, suggesting that the bacterium is a potential target for reversing extraintestinal complications.
Longman's team analyzed the fecal microbiome of inflammatory bowel disease patients with or without spondyloarthritis. Bacteria coated with IgA -- an antibody crucial to mucosal immunity -- were detected. Using several analytic methods, they found that patients with Crohn's disease–associated spondyloarthritis had more IgA-coated E. coli than patients with Crohn's disease alone. These bacteria trigger inflammation that contributes to spondyloarthritis. Based on the findings, scientists may be able to develop new tools to determine the risk that a Crohn's disease patient has to develop spondyloarthritis.
Further experiments showed that these bacteria work through the Th17 cells, a subset of immune cells that have been implicated in the pathogenesis of many autoimmune diseases. Patients with Crohn's disease–associated spondyloarthritis had higher levels of Th17 cells and protein IL-23, a cytokine that promotes Th17 formation.
Ustekinumab, a human antibody that antagonises IL-12 and IL-23 and is originally used to treat psoriasis, has been FDA for the treatment of Crohn's disease recently. This drugs targets the p40 subunit of IL-12 and IL-23, preventing them from binding and activating T-cells.
All this information suggests that it is reasonable to evaluate the effect of anti-IL-23 drugs in Crohn's disease. The study provides a link between Crohn's disease and spondyloarthritis. Although there are still many questions to be answered, the study may guide medical and biologic therapy for Crohn's disease patients. Cusabio provides IL-12, IL-23, and antibodies.