Clinical outcome in IL-10- and IL-10 receptor-deficient patients with or without hematopoietic stem cell transplantation

J Allergy Clin Immunol. 2013 Mar;131(3):825-30. doi: 10.1016/j.jaci.2012.09.025. Epub 2012 Nov 14.

Abstract

Background: Inherited deficiencies of IL-10 or IL-10 receptor (IL-10R) lead to immune dysregulation with life-threatening early-onset enterocolitis.

Objectives: We 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).

Methods: We 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.

Results: Of 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.

Conclusion: Because 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Colitis / diagnosis
  • Colitis / etiology
  • Colitis / genetics
  • Colitis / therapy*
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Deficiency Syndromes / complications
  • Immunologic Deficiency Syndromes / diagnosis
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / therapy*
  • Infant
  • Infant, Newborn
  • Interleukin-10 / deficiency*
  • Male
  • Mutation
  • Receptors, Interleukin-10 / deficiency*

Substances

  • Receptors, Interleukin-10
  • Interleukin-10