Suppression of donor-reactive T cells by pretransplant sera of renal transplant recipients.
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Biomedical subjects
Publications and source records attributed to G Opelz.
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Serial plasma samples of 172 kidney transplant recipients and 42 chronic dialysis patients were evaluated retrospectively in a radioimmunoassay to determine the clinical relevance of plasma neopterin levels. Dialysis patients had a higher neopterin level 196 +/- 82 nmol/L (mean +/- SD) than 70 healthy controls (7 +/- 4 nmol/L). In 45 patients with a completely uneventful postoperative course, elevated pretransplant neopterin levels dropped rapidly within a week to a mean of 30 nmol/L and remained stable thereafter. In 22 outpatients with stable graft function there was a highly significant correlation between 170 paired serum creatinine and plasma neopterin values (r = 0.94). A group of 13 patients had experienced delayed graft function (ATN) without rejection. Their one-week mean neopterin level was 100 nmol/L and continued to drop in parallel with the serum creatinine. Another 15 patients rejected their kidneys irreversibly within 3 weeks-6 of them had extremely high neopterin levels during the rejection process (range 500-1000 nmol/L) that were not seen in other patients. A total of 169 rejection episodes in 43 patients were treated with bolus-dose cortisone. On the day of bolus therapy, both serum creatinine (P less than 0.002) and neopterin (P less than 0.005) were elevated. At 24 hours prior to bolus cortisone therapy, creatinine levels were not significantly elevated, whereas there was a significant rise in plasma neopterin (P less than 0.01). The overall sensitivity of neopterin increase was 86% with a 17% probability of false positives, and the sensitivity was 95% in biopsy-proved rejections. Plasma neopterin appears to be a useful marker for early detection of rejection and for identifying severe rejections that are not responsive to treatment.
An excellent correlation of predicted and observed cadaver kidney graft survival rates was obtained using a nine-factor computer model. A total of 924 recipients for whom a greater than 80% 1-year survival rate was predicted had an observed rate of 84.6%, whereas 179 recipients with a predicted 1-year success rate of less than 40% had an observed rate of 38.2%. Our model gives improved results as compared with previously published methods. We anticipate that the model's predictive power can be further refined, and that patient selection and organ sharing will benefit from the application of sophisticated computer models for the prediction of transplant success.
Of 170 hemophilia patients, 22% had high-titer, 29% had low-titer, and 49% had no antibodies against HTLV-III. The strength of HTLV-III antibodies was correlated significantly with a decreased OKT4/T8 ratio (p less than 0.0005), decreased in vitro response to pokeweed mitogen (p less than 0.025), and elevated serum neopterin (p less than 0.05) and serum IgG (p less than 0.0005). The fraction of patients with abnormal immunological findings was consistently greater among patients with high-titer than among patients with low-titer HTLV-III antibodies. Testing these immunological parameters may be useful for monitoring the breakdown of immune functions leading to AIDS.