Altered immunity as a risk factor for non-Hodgkin lymphoma

This review examines the association between disorders of immunity, including immune deficiency, atopy, and autoimmune disease, and non-Hodgkin lymphoma (NHL). Immune deficiency is one of the strongest known risk factors for NHL. Risk is increased whether the immune deficiency is congenital, iatrogenic, or acquired. Risk of NHL increases with degree of immune deficiency, and there is no evidence of a threshold. In the profoundly immune deficient, NHL is frequently caused by infection with the ubiquitous EBV. Whether mild, subclinical immune deficiency is related to increased NHL risk is unknown. There is inconsistent evidence that atopic conditions, such as asthma, hayfever, and eczema, characterized by an immune response that is skewed toward Th2, are associated with a decreased risk of NHL. These data come mainly from case-control studies. Concern has been expressed that the association may be due to reverse causality if early symptoms of NHL include a lessening of atopic manifestations. Case-control and cohort studies of people with autoimmune conditions have generally shown that rheumatoid arthritis, systemic lupus erythematosis, and Sjogren's disease are associated with increased NHL risk. It seems to be the intensity of the inflammatory disease rather than its treatment which is related to increased risk of NHL. The study of altered immunity as a cause of NHL in case-control studies is limited by the fact that development of NHL in itself leads to altered immunity. Cohort studies of the role of altered immunity should be a top priority in epidemiologic studies of NHL etiology.