The diagnosis of cardiac allograft rejection is currently based on endomyocardial biopsy and histologic evaluation. Since the introduction of cyclosporine, cardiac biopsy has been recognized as the only reliable method of diagnosis. From July 1985 to June 1986, 22 transplant patients were studied during the early posttransplant period to evaluate other characteristics of allograft rejection. The immunosuppressive protocol included cyclosporine, azathioprine, prednisone, and prophylactic rabbit antithymocyte globulin. Acute rejection was established by standard histologic criteria. Twenty-four positive and 123 negative biopsy findings were obtained. Clinical variables (age, sex, immunosuppressive regimen, cyclosporine dosage, ECG voltage), biologic variables (level of cyclosporine, white blood cells, blood urea nitrogen, creatinine, bilirubin, prolactin, urinary polyamines, blood type, HLA typing), and immunologic variables (T-cell subsets) were analyzed in regard to the histologic diagnosis of acute rejection. Four variables (WBC, prolactin, total urinary polyamines, N-acetyl putrescine) were found to have a significant univariate association with acute rejection. These variables were studied by multivariate discriminant analysis. The only factors found to have independent predictive value for acute rejection were prolactin and N-acetyl putrescine peaks occurring before acute rejection. When we used these factors, a discriminant function correctly predicted acute rejection episodes, as well as negative biopsy results, in 74% of the cases in this group of patients.

Biopsy↗

PubMedDate not supplied

Urinary polyamines are noninvasive markers of heart allograft rejection.

Histologic evaluation of the heart allograft biopsy is currently the generally accepted method to monitor for rejection after transplantation. A noninvasive marker of host prerejection immunologic activation might be a useful clinical tool and provide the basis for a more continuous evaluation than is available with the biopsy technique. Urinary polyamine levels, in the context of immune activation, may fluctuate as an indicator of lymphocyte proliferation and organ rejection. To test this hypothesis cervical heterotopic heart transplantation was performed in six dogs that did not receive immunosuppression therapy. Daily percutaneous transmural biopsy of the transplanted heart and urine samples were collected. Urinary polyamines were measured by high-pressure liquid chromatography. Between 2 and 4 days after transplantation all allografts showed a histologic picture of mild to moderate rejection. The urinary excretion of total polyamines and putrescine fraction increased during the rejection process after transplantation, attaining a maximum from the first to the third day after operation. This early elevation suggests that urinary polyamines are markers of immune activation and unmodified heart allograft rejection. Further studies need to be done to define a potential clinical application of urinary polyamines as markers of cellular metabolic activity of the immune system and allograft rejection.

Animals↗

PubMedDate not supplied

Prolactin as a marker of rejection in human heart transplantation.

Prolactin has been shown to play a role in the modulation of the immune system. In addition, recent laboratory evidence suggests that circulating prolactin might fluctuate as a function of immunologic events. To evaluate the role of prolactin as a predictor of rejection, 22 heart and heart-lung transplant patients were studied from July 1985 to May 1986. Daily plasma prolactin levels were measured by radioimmunoassay. Endomyocardial biopsy and histologic evaluation of the allografts were used to define rejection episodes. Thirteen of 14 documented rejection episodes were preceded by a specific elevation of circulating prolactin. A significant elevation of prolactin occurred 6 and 8 days before 14 rejection episodes that were diagnosed by biopsy but not before 109 biopsies were taken that had negative results. The normal values for circulating prolactin are defined by a preoperative mean in a range of 0 to 15 ng/ml (95% confidence limit). The sensitivity of prolactin to predict rejection is 79%, the specificity is 92%, and the positive predictive value is 61%. A large data variability gives a low accuracy to the test as a predictor of allograft rejection. To be useful clinically, the accuracy needs to be improved through a better understanding of prolactin physiology and its relation to the immune system.

Adult↗