Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease.
Griffin H., Ceron-Gutierrez L., Gharahdaghi N., Ebrahimi S., Davies S., Loo PS., Szabo A., Williams E., Mukhopadhyay A., McLoughlin L., Irwin S., Travis S., Klenerman P., Bunn S., Cant AJ., Hambleton S., Uhlig HH., Doffinger R.
We discovered high-titer neutralizing autoantibodies against interleukin-10 in a child with infantile-onset inflammatory bowel disease (IBD), a phenocopy of inborn errors of interleukin-10 signaling. After B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn. A second child with neutralizing anti-interleukin-10 autoantibodies had a milder course of IBD and has been treated without B-cell depletion. We conclude that neutralizing anti-interleukin-10 autoantibodies may be a causative or modifying factor in IBD, with potential implications for therapy. (Funded by the National Institute for Health and Care Research and others.).