Autoantibodies are misdirected antibodies produced by the immune system that target the body’s own tissues—in this case, the interleukin-10 signaling pathway—and not pathogens. This pathway is a key anti-inflammatory mechanism of the immune system that dampens excessive immune responses to prevent tissue damage. New research findings show that patients with inflammatory bowel disease develop autoimmune reactions against a key player in the immune system: interleukin-10. This leads to uncontrolled inflammation. 

The research team analyzed approximately 4,900 patients with chronic inflammatory bowel diseases. They used a cellular interleukin-10 reporter assay and an enzyme-lmmuno assay  to detect neutralizing interleukin-10 autoantibodies in the patients’ serum samples.  About 3.5% of the patients had antibodies against IL-10 that are not found in unaffected individuals. Many of those with autoantibodies also carried a gene variant of an immune gene known as HLA-DRB1*01:03 (Human Leukocyte Antigen - DR isotype 1). This is a group of cell surface receptors for a protein molecule that plays a key role in the adaptive immune system. HLA-DRB1*01:03 is the strongest genetic risk factor associated with ulcerative colitis.

The authors are convinced that their findings can help to improve diagnostic tests for this type of chronic inflammatory bowel disease as well as therapies for those who carry anti-IL-10 antibodies.

Original paper:
Gharahdaghi N, Yeh PJ, Ceron-Gutierrez L, Griffin H, Gordon H, Jayamanne C, Fracchia A, Chong AY, Walsh A, Brain O, Baker K, Kockelbergh H, Luo Y, Guevara Becerra M, Vadakethala K, Coy M, Kabiri L, Barnardo M, Dunachie S, Kronsteiner B, Adams A, Fowler D, Zhang Q, Fachal L, Anderson CA, Desoki R, Vestergaard MV, Larsen L, Wyatt NJ, Lees RD, Mulligan RJ, Dong C, Sharip MT, Faustini SE, Shields A, Pakpoor J, Naz B, Richter A, Satsangi J, Lamb CA, Parkes M, Powrie F, Mentzer AJ, Sazonovs A, Jess T, Klenerman P, Travis S, Hambleton S, Doffinger R, Uhlig HH. Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease. N Engl J Med. 2026 Jun 11;394(22):2212-2222. doi: 10.1056/NEJMoa2513654. PMID: 42269151.

Further information:
1. Zhang Q, Shakweh E, Sharip MT, Zare B, Roberts C, Wyatt NJ, Clough J, Bewshea C, Garwany OE, Lees R, Mukhtar S, Rehman H, Thistle H, Mulligan R, Taylor M, Raymode P, Hamilton B, Noor NM, Morda F, Taylor M, Gyanwali M, Tobi O, Kateroglou S, Von Hagt S; UK IBD Genetics Consortium; NIHR IBD BioResource; Sebastian S, Hart A, Keylock L, Pele L, Lees CW, Raine T, Lamb CA, Anderson CA, Ahmad T, Uhlig H, Parkes M, Fachal L, Kennedy NA, Lee JC. (2026). HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype-phenotype association study. Lancet Gastroenterol Hepatol. 2026, Jun 15: S2468-1253(26)00113-5. doi: 10.1016/S2468-1253(26)00113-5. Epub ahead of print. PMID: 42296978.
2. https://www.labroots.com/trending/cell-and-molecular-biology/30664/researchers-cause-inflammatory-bowel-disease
3. https://www.ndm.ox.ac.uk/team/holm-uhlig