Immune deficiencies, infection, and systemic immune disordersClinical outcome in IL-10– and IL-10 receptor–deficient patients with or without hematopoietic stem cell transplantation
Section snippets
Patients
We enrolled a total of 40 patients in this study with informed consent and approval by the responsible local ethics committees. The study patients represented a subgroup of pediatric patients with IBD in whom another defined primary immunodeficiency had been ruled out and who presented with onset of severe endoscopically and histopathologically confirmed colitis within the first 4 years of life. All had resistance to immunosuppressive therapy. All but one of the patients' families had possible
Patients with mutations affecting IL-10 and IL-10R
In our cohort of 40 new patients selected as previously described, 7 (18%) had molecular defects in IL-10 signaling, all with mutations in IL10RA or IL10RB, the genes encoding the IL-10R components IL-10 receptor α chain (IL-10R1) and IL-10 receptor β chain (IL-10R2), respectively (Table I).2
Patient 1 showed a homozygous point mutation in exon 3 of IL10RA (c.350G>A) leading to an amino acid exchange from arginine to histidine at position 117 (Arg117His) in the IL-10R1 protein. Patient 2
Discussion
We analyzed a cohort of 40 patients with early-onset IBD and identified 7 (18%) with mutations in the genes encoding IL-10R: IL10RA (encoding IL-10R1) and IL10RB (encoding IL-10R2; previously published mutations are summarized in Table E3 in this article's Online Repository at www.jacionline.org). We did not see any genotype-phenotype correlations in this cohort of patients. In contrast to the other 33 pediatric patients without mutations, IL-10/IL-10R–deficient patients had a very early onset
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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).
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.