A Mendelian predisposition to B cell lymphoma caused by IL-10R deficiency
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.
- Copyright © 2005 American Society of Hematology