Clinical outcome in IL-10– and IL-10 receptor–deficient patients with or without hematopoietic stem cell transplantation - 27/02/13
Corresponding author: Erik-Oliver Glocker, MD, Institute of Medical Microbiology and Hygiene, University Medical Center Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany.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 ⍺ 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.
Le texte complet de cet article est disponible en PDF.Key words : IL-10, IL-10 receptor, enterocolitis, mutations, colectomy, hematopoietic stem cell transplantation
Abbreviations used : CMV, FOXP3, HSCT, IBD, IL-10R, IL-10R1, IL-10R2, NEMO, NK, XIAP
Plan
| Supported by NEOPICS, the Canadian National Early Onset Pediatric Cohort Study (to A.M.M.), grants from the European Commission Marie Curie Excellence program (MEXT-CT-2006-042316, to B.G.), EURO-PADNet (to B.G.), Marie Curie Actions CIG (294253, to E.-O.G.), the USA National Institutes of Health/NCRR UCSF-CTSI (grant no. UL1 RR024131), the UCSF Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies (to J.M.P.), and the German Federal Ministry of Education and Research (BMBF 01 EO0803). |
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| Disclosure of potential conflict of interest: K. R. Engelhardt has received a grant from the German Federal Ministry of Education and Research (BMBF 01 EO0803). C. Klein has received a grant from the Care-for-Rare Foundation. J. M. Puck has received a grant from the National Institutes of Health. B. Grimbacher has received a grant from the European Community 6th and 7th Framework Programmes, a Marie Curie Excellence grant, and a grant from the German Federal Ministry of Education and Research. E.-O. Glocker has received a Career Integration grant from the European Commission/Marie-Curie Actions. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 3
P. 825 - mars 2013 Retour au numéro
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