Lymphoma risks in populations with altered immunity--a search for mechanism

There have been numerous studies of lymphoma incidence in patient populations having diseases or taking medications that result in altered immunity. While many of these have uncovered substantially elevated risks, little has been done to use these observations to gain insights into the mechanisms of lymphomagenesis. Speculation about mechanism has centered on either immunosuppression or immunostimulation. The patterns of risk among kidney transplant recipients (higher risks for those receiving cadaveric grafts, having multiple transplants, or having received transplants in the earlier years of transplantation) favor the immunostimulation hypothesis. Likewise, the higher lymphoma risk associated with indices of increasing severity of disease among patients with sicca syndrome also support the role of immunostimulation over that of immunosuppression. However, an ordering of many of the more extensively studied conditions with altered immunity on the basis of the relative risk of lymphoma associated with these conditions reveals a pattern of risk which is not completely consistent with the level of either immune suppression or immune stimulation. Perhaps we have reached a point where epidemiologists working with laboratory and clinical immunologists can discern a more sophisticated underlying mechanism than the crude concepts of immunosuppression or immunostimulation that would explain the markedly differing lymphoma risks seen in various groups with marked immune abnormalities. If so, markers of more subtle alterations in this mechanism might be profitably explored for their role in lymphoma in general and as a tool to define the environmental causes of the epidemic increases.