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

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 and Alain Fischer

Key points

  • 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.


Monogenic interleukin (IL)-10 and IL-10 receptor (IL-10R) deficiencies cause very early-onset, severe inflammatory bowel disease. Here, we report that five patients with an IL-10R1 (n=1) or IL-10R2 (n=4) deficiency developed B cell non-Hodgkin's lymphoma between the ages of 5 and 6 years (which were recurrent in one 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 NF-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.

  • Submitted June 13, 2013.
  • Accepted August 14, 2013.