A Mendelian predisposition to B-cell lymphoma caused by IL-10R deficiency.

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.

• Authors: Bénédicte Neven, Emilie Mamessier, Julie Bruneau, Sophie Kaltenbach, Daniel Kotlarz, Felipe Suarez, Julien Masliah-Planchon, Katy Billot, Danielle Canioni, Pierre Frange, Isabelle Radford-Weiss, Vahid Asnafi, Dhaarini Murugan, Christine Bole, Patrick Nitschke, Olivier Goulet, Jean-Laurent Casanova, Stéphane Blanche, Capucine Picard, Olivier Hermine, Frederic Rieux-Laucat, Nicole Brousse, Frederic Davi, Véronique Baud, Christoph Klein, Bertrand Nadel, Frank Ruemmele, Alain Fischer
• Journal: Blood (Blood) Vol. 122 Issue 23 Pg. 3713-22 (Nov 28 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 24089328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• Interleukin-10 Receptor alpha Subunit
• Interleukin-10 Receptor beta Subunit
• NF-kappa B
• Interleukin-10

Topics

• Adolescent
• Age of Onset
• Child
• Child, Preschool
• Female
• Gene Expression Profiling
• Genes, rel
• Genetic Predisposition to Disease
• Germinal Center (immunology, pathology)
• Humans
• Inflammatory Bowel Diseases (complications, genetics, immunology)
• Interleukin-10 (metabolism)
• Interleukin-10 Receptor alpha Subunit (deficiency, genetics)
• Interleukin-10 Receptor beta Subunit (deficiency, genetics)
• Lymphoma, B-Cell (etiology, genetics, immunology)
• Lymphoma, Large B-Cell, Diffuse (etiology, genetics, immunology)
• Male
• Mutation
• NF-kappa B (metabolism)
• Pedigree
• Signal Transduction