Lymphoid neoplasms include many different disease entities with distinct cells of origin, pathologies, risk factor profiles, and prognoses1
Immune dysregulation is thought to play a major role in lymphomagenesis as evidenced by the increased risk of certain lymphomas following organ transplant, infections, immunodeficiency states, and autoimmune conditions.2
Autoimmune diseases also comprise a broad variety of conditions characterized by dysregulation in various components of the immune response leading to loss of tolerance to self-antigens. The association of lymphoma and autoimmunity was recognized early on from case reports of autoimmune diseases preceding or co-occurring with lymphoma, and mouse strains showing association of autoimmune disease and lymphoma.3
Over the last three decades, there has been consistent evidence from population-based case-control and cohort studies that certain autoimmune diseases (especially rheumatoid arthritis (RA), Sjögren’s syndrome, and systemic lupus erythematosus (SLE) are associated with an increased risk of developing lymphoma.4
Explanations for these associations include the role of chronic immune stimulation, treatment for autoimmune disease, and shared genetic and/or environmental factors. A unifying model argues that both autoimmunity and lymphomas result from inhibitions (as a result of germline- and somatic mutations) of normal pathways that keep uncontrolled lymphocyte growth in check.5
Large population-based studies of lymphoma patients have revealed patterns of associations that suggest mechanisms for lymphomagenesis. However, studies have been limited by the rarity and heterogeneity of both autoimmune diseases and lymphomas. Additional challenges include the limitation of many studies to patients who were hospitalized due to autoimmune disease, latency of lymphoma development following autoimmune disease, the role of treatment for certain autoimmune diseases, and autoimmunity occurring as a complication of lymphomas.
In this report, we review the current state of knowledge relevant to the associations between autoimmune diseases and lymphomagenesis including our recent studies based on data from Scandinavia and from U.S. Veterans and other relevant literature as well as what these associations imply about the etiology of lymphomas. We also point out gaps in the literature and speculate about future directions for new studies.