Abstract
Monogenic interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiencies cause very early onset severe inflammatory bowel disease. Here, we report that 5 patients with an IL-10R1 (n = 1) or IL-10R2 (n = 4) deficiency developed B-cell non-Hodgkin lymphoma between the ages of 5 and 6 years (which was recurrent in 1 patient). These lymphomas had some of the characteristics of diffuse large B-cell lymphomas and contained monoclonal, Epstein-Barr virus-negative germinal center B cells. The tumors displayed a remarkably homogeneous signature, with original activation of the nuclear factor κB pathway and a decrease in intratumor T-cell infiltration. Hence, IL-10R deficiency is associated with a high risk of developing B-cell lymphoma. Our results revealed an unexpected role of the IL-10R pathway in lymphomagenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Age of Onset
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Child
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Child, Preschool
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Female
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Gene Expression Profiling
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Genes, rel
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Genetic Predisposition to Disease
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Germinal Center / immunology
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Germinal Center / pathology
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Humans
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Inflammatory Bowel Diseases / complications
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Inflammatory Bowel Diseases / genetics
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Inflammatory Bowel Diseases / immunology
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Interleukin-10 / metabolism
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Interleukin-10 Receptor alpha Subunit / deficiency*
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Interleukin-10 Receptor alpha Subunit / genetics*
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Interleukin-10 Receptor beta Subunit / deficiency*
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Interleukin-10 Receptor beta Subunit / genetics*
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Lymphoma, B-Cell / etiology
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Lymphoma, B-Cell / genetics*
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Lymphoma, B-Cell / immunology*
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Lymphoma, Large B-Cell, Diffuse / etiology
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Lymphoma, Large B-Cell, Diffuse / genetics
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Lymphoma, Large B-Cell, Diffuse / immunology
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Male
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Mutation
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NF-kappa B / metabolism
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Pedigree
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Signal Transduction
Substances
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IL10 protein, human
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Interleukin-10 Receptor alpha Subunit
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Interleukin-10 Receptor beta Subunit
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NF-kappa B
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Interleukin-10