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

• Published in: Blood Vol. 122; no. 23; pp. 3713 - 3722
• Main Authors: Neven, Bénédicte, Mamessier, Emilie, Bruneau, Julie, Kaltenbach, Sophie, Kotlarz, Daniel, Suarez, Felipe, Masliah-Planchon, Julien, Billot, Katy, Canioni, Danielle, Frange, Pierre, Radford-Weiss, Isabelle, Asnafi, Vahid, Murugan, Dhaarini, Bole, Christine, Nitschke, Patrick, Goulet, Olivier, Casanova, Jean-Laurent, Blanche, Stéphane, Picard, Capucine, Hermine, Olivier, Rieux-Laucat, Frederic, Brousse, Nicole, Davi, Frederic, Baud, Véronique, Klein, Christoph, Nadel, Bertrand, Ruemmele, Frank, Fischer, Alain
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.11.2013; American Society of Hematology
• Subjects: Adolescent; Age of Onset; Cancer; Child; Child, Preschool; Female; Gene Expression Profiling; Genes, rel; Genetic Predisposition to Disease; Germinal Center - immunology; Germinal Center - pathology; Humans; Immunology; Immunotherapy; Inflammatory Bowel Diseases - complications; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - immunology; Interleukin-10 - metabolism; Interleukin-10 Receptor alpha Subunit - deficiency; Interleukin-10 Receptor alpha Subunit - genetics; Interleukin-10 Receptor beta Subunit - deficiency; Interleukin-10 Receptor beta Subunit - genetics; Life Sciences; Lymphoma, B-Cell - etiology; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, Large B-Cell, Diffuse - etiology; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - immunology; Male; Mutation; NF-kappa B - metabolism; Pedigree; Signal Transduction
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2013-06-508267

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. •Human inherited IL-10 receptor deficiency is associated with a very high risk of non-EBV–related diffuse large B-cell lymphoma.•IL-10 signaling may be involved in the immune control of germinal center B-cell lymphoma.