A New England Journal of Medicine study of more than 4,900 people with inflammatory bowel disease links autoantibodies against interleukin-10 to a long-known genetic risk variant, pointing toward a possible blood test and targeted treatment.

Researchers from the University of Oxford, Newcastle University and Cambridge University Hospitals NHS Foundation Trust report in the New England Journal of Medicine that some people with inflammatory bowel disease (IBD) produce antibodies that block interleukin-10 (IL-10), a protein that helps keep inflammation in check. The team examined more than 4,900 people with IBD, which includes Crohn's disease and ulcerative colitis, and found elevated levels of these neutralising antibodies in about 3.5% of patients, in both conditions but not in healthy individuals. Based on UK prevalence, they estimate that 15,000 to 20,000 patients in the country could carry them.

The study also links the antibodies to a genetic variant called HLA-DRB1*01:03, which Oxford scientists tied to a severe form of IBD 30 years ago without knowing how it caused disease. People carrying the variant were substantially more likely to develop antibodies against IL-10, which the researchers say helps explain the mechanism. Sophie Hambleton of Newcastle University said the work builds on earlier findings that inherited defects in IL-10 or its receptor cause severe IBD in young children, and that antibodies against IL-10 had been seen mimicking that effect in two girls with colitis.

The researchers say the findings suggest IBD includes several biologically distinct conditions and could lay the groundwork for a blood test to identify patients whose disease is linked to these antibodies, and for treatments aimed at the antibodies or the cells that make them. Those are possibilities rather than established therapies, and the reported results do not yet show that any such treatment works. Senior author Holm Uhlig of Oxford said the study opens the door to new treatments, while Cambridge's Rainer Doffinger said early identification could reduce reliance on costly ongoing therapy. The work was funded through NIHR Biomedical Research Centres in Oxford, Cambridge and Newcastle.