Nima Gharahdaghi, Pai‐Jui Yeh, Lourdes Ceron‐Gutierrez, H Griffin, Hannah Gordon, Chamara Jayamanne, Alice Fracchia, Amanda Y. Chong, Alissa Walsh, Oliver Brain, Katherine Baker, Hannah Kockelbergh, Yang Luo, Martha Guevara Becerra, Katherine Vadakethala, Madeleine Coy, Ladan Kabiri, Martin Barnardo, Susanna Dunachie, Barbara Kronsteiner, Anna Adams, Darren Fowler, Qian Zhang, Laura Fachal, Carl A. Anderson, R Desoki, Marie Vibeke Vestergaard, Lone Larsen, Nicola J Wyatt, Robert Lees, Robert J. Mulligan, Chaonan Dong, Mohmmed Tauseef Sharip, S Faustini, Adrian Shields, Julia Pakpoor, Bushra Naz, Alex Richter, Jack Satsangi, Christopher A. Lamb, M Parkes, Fiona Powrie, Alexander J. Mentzer, Aleksejs Sazonovs, Tine Jess, P Klenerman, Simon Travis, Sophie Hambleton, Rainer Döffinger, Holm H. Uhlig
BACKGROUND: Neutralizing autoantibodies against interleukin-10 can result in a phenocopy of monogenic defects of interleukin-10 signaling in children and may be associated with inflammatory bowel disease (IBD). The allele HLA-DRB1*01:03 is the strongest genetic risk factor for ulcerative colitis. METHODS: We used a cellular interleukin-10 reporter assay and a confirmatory competitive enzyme-linked immunosorbent assay to assess neutralizing interleukin-10 autoantibodies in serum samples obtained from patients with IBD in the Oxford and U.K. IBD BioResource cohorts and from persons without IBD (controls). An in vitro cytokine-release bioassay was performed in a subgroup of patients to assess interleukin-10, interleukin-23, interleukin-1β, tumor necrosis factor, and interleukin-6. We performed HLA association analysis using imputation and high-resolution sequencing. RESULTS: ). CONCLUSIONS: Neutralizing interleukin-10 autoantibodies were present in a subgroup of patients with IBD and were strongly associated with HLA-DRB1*01:03. (Funded by the National Institute for Health and Care Research and others.).