Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease

Helen Griffin; Lourdes Ceron-Gutierrez; Nima Gharahdaghi; Soraya Ebrahimi; Sophie Davies; Peh Sun Loo; Andras Szabo; Eleri Williams; Anirban Mukhopadhyay; Louise McLoughlin; Steven Irwin; Simon Travis; Paul Klenerman; Su Bunn; Andrew J Cant; Sophie Hambleton; Holm H Uhlig; Rainer Doffinger

doi:10.1056/NEJMoa2312302

Neutralizing Autoantibodies against Interleukin-10 in Inflammatory Bowel Disease

N Engl J Med. 2024 Aug 1;391(5):434-441. doi: 10.1056/NEJMoa2312302.

Authors

Helen Griffin¹, Lourdes Ceron-Gutierrez¹, Nima Gharahdaghi¹, Soraya Ebrahimi¹, Sophie Davies¹, Peh Sun Loo¹, Andras Szabo¹, Eleri Williams¹, Anirban Mukhopadhyay¹, Louise McLoughlin¹, Steven Irwin¹, Simon Travis¹, Paul Klenerman¹, Su Bunn¹, Andrew J Cant¹, Sophie Hambleton¹, Holm H Uhlig¹, Rainer Doffinger¹

Affiliation

¹ From the Immunity and Inflammation Theme, Newcastle University Translational and Clinical Research Institute (H.G., S.H.), and the Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust (P.S.L., E.W., A.M., A.J.C., S.H.), Newcastle upon Tyne, the Department of Clinical Biochemistry and Immunology, Cambridge University Hospital (L.C.-G., S.E., S.D., R.D.), and the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (R.D.), Cambridge, the Translational Gastroenterology Unit (N.G., S.T., P.K., H.H.U.), the Kennedy Institute of Rheumatology (S.T.), the NIHR Oxford Biomedical Research Centre (S.T., P.K., H.H.U.), and the Department of Pediatrics (H.H.U.), University of Oxford, Oxford, the Department of Pediatric Gastroenterology, Royal Belfast Hospital for Sick Children (A.S., L.M.), and the Department of Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust (S.I.), Belfast, and the Department of Pediatric Gastroenterology, Royal Aberdeen Children's Hospital, Aberdeen (S.B.) - all in the United Kingdom; and the Pediatric Gastroenterology Department, Pál Heim National Pediatric Institute, Budapest, Hungary (A.S.).

Abstract

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B-cell-depletion therapy and an associated decrease in the anti-interleukin-10 titer, conventional IBD therapy could be withdrawn.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.).

Publication types

Case Reports

MeSH terms

Antibodies, Neutralizing* / blood
Antibodies, Neutralizing* / immunology
Autoantibodies* / blood
Autoantibodies* / immunology
B-Lymphocytes / drug effects
B-Lymphocytes / immunology
Child, Preschool
Drug Therapy, Combination / methods
Female
Glucocorticoids / administration & dosage
Humans
Immunoglobulins, Intravenous / administration & dosage
Infant
Inflammatory Bowel Diseases* / blood
Inflammatory Bowel Diseases* / diagnosis
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / immunology
Infliximab / administration & dosage
Interleukin-10* / immunology
Male
Severity of Illness Index
Treatment Outcome

Substances

Antibodies, Neutralizing
Autoantibodies
Interleukin-10
Immunoglobulins, Intravenous
Glucocorticoids
Infliximab

Abstract

Publication types

MeSH terms

Substances

Grants and funding