Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics

Common variable immunodeficiency represents the largest group of primary immunodeficiency patients. The variable clinical manifestations include an increased susceptibility to chronic infections, granulomatous disease and the lymphoproliferative predisposition to develop lymphoma. This review discusses the latest insights into common variable immunodeficiency and uses common variable immunodeficiency as a model to examine the links between immunodeficiency and chronic infections in causing lymphoma.

Newly identified disease genes within the common variable immunodeficiency population, have advanced the understanding of human immunodeficiency and the molecular basis of B-cell biology. Refined laboratory techniques have better defined this heterogeneous condition by classifying the underlying B-cell and T-cell abnormalities. New sensitive methods have also identified the presence of persistent infections that may play a role in the development of lymphoma.

There are several reasons for an increased risk of lymphoma in common variable immunodeficiency patients. These include genetics, immune dysregulation, radiosensitivity and chronic infections such as Helicobacter pylori, human herpes virus type 8 and cytomegalovirus. Chronic infections may enhance the development of lymphoma in an antigen specific manner. The interaction between chronic infections and the development of lymphoma is still unclear but studies to clarify this may lead to prevention measures and lymphoma reduction strategies.