1. Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation.
- Author
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Engelhardt, Karin R, Shah, Neil, Faizura-Yeop, Intan, Kocacik Uygun, Dilara F, Frede, Natalie, Muise, Aleixo M, Shteyer, Eyal, Filiz, Serkan, Chee, Ronnie, Elawad, Mamoun, Hartmann, Britta, Arkwright, Peter D, Dvorak, Christopher, Klein, Christoph, Puck, Jennifer M, Grimbacher, Bodo, and Glocker, Erik-Oliver
- Subjects
Humans ,Colitis ,Immunologic Deficiency Syndromes ,Interleukin-10 ,Hematopoietic Stem Cell Transplantation ,Mutation ,Adult ,Child ,Child ,Preschool ,Infant ,Infant ,Newborn ,Female ,Male ,Receptors ,Interleukin-10 ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Human ,Rare Diseases ,Transplantation ,Pediatric ,Stem Cell Research - Nonembryonic - Non-Human ,Clinical Research ,Regenerative Medicine ,Digestive Diseases ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Inflammatory and immune system ,IL-10 ,IL-10 receptor ,enterocolitis ,mutations ,colectomy ,hematopoietic stem cell transplantation ,Immunology ,Allergy - Abstract
BackgroundInherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threatening early-onset enterocolitis.ObjectivesWe sought to gather clinical data of IL-10/IL-10R-deficient patients and devise guidelines for diagnosis and management, including hematopoietic stem cell transplantation (HSCT).MethodsWe enrolled 40 patients with early-onset enterocolitis and screened for mutations in IL10/IL10R using genetic studies, functional studies, or both of the IL-10 signaling pathway. Medical records of IL-10/IL-10R-deficient patients were reviewed and compiled.ResultsOf 40 patients, we identified 7 with novel mutations, predominantly in consanguineous families with more than 1 affected member. IL-10/IL-10R-deficient patients had intractable enterocolitis, perianal disease, and fistula formation. HSCT was carried out in 2 patients with IL-10 deficiency and 1 patient with IL-10R α chain deficiency and proved to be an effective therapy, leading to rapid improvement of clinical symptoms and quality of life.ConclusionBecause the defect in patients with IL-10/IL-10R deficiency resides in hematopoietic lineage cells and their colitis is resistant to standard immunosuppressive therapy, HSCT should be considered early as a potentially curative therapeutic option.
- Published
- 2013