Development of anergy to delayed-type hypersensitivity antigens following renal allotransplantation

A study is reported of patients receiving 180 renal allotransplants and at risk for 1 or more years who had pretransplant and posttransplant skin tests using delayed type hypersensitivity (DTH) recall antigens. Pretransplant skin testing revealed an incidence of 14% anergic patients prior to a first transplant, and 35% were anergic prior to a second allograft. There was a statistically significant correlation between pretransplant anergy and age, as well as a significant correlation between pretransplant anergy and time of dialysis-dependent uremia. The conversion to the anegic state posttransplant in those patients with surviving allografts increased annually for the first 5 years as a linear function, with 69% of the population at risk with their first transplant exhibiting anergy by 5 years. In those patients receiving second renal transplants, all were anergic by 4 years posttransplant. In vitro tests of lymphocyte function using mitogen stimulation did not reveal significant differences between anergic and responsive patients. In this series of 180 allografts there were 14 late deaths. Eleven of these were in anergic patients and in 10 instances were related to sepsis or malignancy. Three patients who were skin-test responsive at the time of death died from cardiovascular causes. It is concluded that there is an increasing risk of the development of anergy to DTH antigens posttransplant and that the type of late mortality may be marked by this hyporeactive state.