Schulak Ja

Transfusion reactions in donor-specific blood transfusion patients resulting from transfused maternal antibody.

2 observations de transfusions de sang du donneur (mere) avant transplantation renale ayant provoque des reactions (urticaire, nausee, dyspnee). Ces reactions sont attribuees a la presence danticorps dans le plasma de la mere. Les transfusions suivantes, faites apres elimination du plasma, sont tolerees normalement

Failure of cyclosporine to prevent in vivo T cell priming in man. Studies in allogeneic spleen transplantation

Cyclosporine is a potent new immunosuppressive agent utilized in clinical organ transplantation. Available evidence suggest that it interferes with the secretion of interleukin-2. However, the long term efficacy of cyclopsorine in preventing allograft rejection may depend on a relative sparing of suppressor cells early in the allogeneic response, allowing them to mature and effect a state of operational tolerance. If this is the case, cyclosporine must not affect antigen priming or recognition. Two patients in our center underwent allogensic spleen transplant in conjunction with renal and pancreatic transplant. Both patients were treated with therapeutic levels of cyclosporine during the course of transplant. Neither developed any clinical signs of renal or pancreatic transplant rejection. Both patients developed graft-versue-host disease and eventually required allogeneic (donor) splenectomy. Studies performed on the splenocytes recovered from these specimens demonstrate alloantigen-specific cytotoxic T cell precursors. These studies demonstrate that although cyclosporine can prevent allograft rejection it does not necessarily prevent or ameliorate graft-versus-host disease. Furthermore, cyclosporine does not prevent in vivo T cell priming of alloantigen recognition. The primed cytotoxic precursors can be expanded in the presence of exogenous interleukin-2 to become fully active cytoxic cells.

Results of conversion from cyclosporine to azathioprine in cadaveric renal transplantation.

Between December 1983 and August 1985, 110 cadaver transplants were performed at our institution. All were started on cyclosporine (CsA) and prednisone (P) for immunosuppressive therapy. Of the 110 patients, 46 were converted from CsA to azathioprine (AZA) for a variety of reasons (cost, toxicity, patient preference, prolonged dysfunction posttransplant, or nonresponsive rejection). The course and outcome of these patients are described. The only group of patients who had consistent benefit and stable course following the CsA-to-AZA switch were primary cadaver transplants with stable renal function (serum creatinine less than 2 mg/dl) who were converted an average of 7.97 months posttransplant. All other groups of patients had severe problems or graft loss postconversion.

Effect of postmortem ischemia on the function of adult rat islets following pancreatic transplantation

Pancreata from adult rats were subjected to in situ postmortem ischemia at ambient temperature for between 90 and 360 minutes before syngeneic transplantation into diabetic recipients. Islet function, determined by recipient blood glucose and intravenous glucose tolerance tests, was not significantly different from that observed in nonischemic controls after up to 300 minutes of such an insult. Transplantation led to death of pancreata subjected to 360 minutes of ischemia in four or five recipients. Clinical and experimental implications are discussed.

Graft irradiation abrogates graft-versus-host disease in combined pancreas-spleen transplantation.

A model of combined pancreas-spleen transplantation (PST) was studied in LBN F1 recipients of Lewis grafts in order to evaluate the efficacy of pretransplant graft irradiation in preventing lethal graft-versus-host disease (GVHD). Recipients of unmodified PST uniformly developed severe GVHD and died (MST = 16.7 +/- 3.8 days). Whole body donor irradiation with either 500 or 250 rad prevented lethal GVHD. Similarly, ex vivo graft irradiation with either 1000 or 500 rad also resulted in normal weight gain, graft function, and host survival for the 6-week study period. Conversely, delay of graft irradiation until 3 days after transplantation failed to prevent this complication (MST = 15.8 +/- 3.7 days). Recipients of irradiated grafts displayed glucose tolerance tests that were identical to those in the control group indicating that the doses of radiation employed in these experiments were not deleterious to islet function. Irradiated spleen grafts appeared histologically normal at 6 weeks after transplantation. Cells derived from these grafts failed to stimulate lymph node enlargement in a popliteal lymph node assay for GVHD, suggesting that these spleens may have become repopulated with host cells. These experiments confirm that PST has the potential to cause lethal GVHD and suggest that pretransplant graft irradiation may be used to prevent its occurrence.

The effect of warm ischemia and cold-storage preservation on rat pancreas transplantation☆

Pancreatic isografts subjected to preharvest warm ischemia as well as cold-storage preservation in Collins solution were studied after transplantation into diabetic rats to determine whether warm ischemia will limit the ability to preserve pancreas grafts for transplantation. Warm ischemic periods of up to 2 hr did not alter islet function as measured by daily glucose levels and response to intravenous glucose challenge. Likewise, hypothermic preservation of nonischemic pancreata was also well tolerated for up to 24 hr. However, the combination of preharvest warm ischemia and cold storage was deleterious. Whereas 60 min of warm injury coupled with 12 hr of cold storage resulted in successful transplantation in 86% of recipients, lengthening the duration of either warm or cold ischemia uniformly resulted in nonfunctioning grafts. Thus while islet function in the transplanted pancreas is very tolerant of warm ischemia alone, these studies suggest that it should be kept to a minimum if cold storage preservation is to be used.

Cyclosporine abrogation of second-set rejection: Dependence upon major histocompatibility complex disparity☆

The purpose of these experiments was to evaluate the use of cyclosporine (CyS) in preventing accelerated rejection in donor-specific presensitized hosts by comparing its efficacy in donor-recipient strain combinations that were either haploidentical or completely mismatched at the major histocompatibility complex (MHC). Lewis X Brown Norway F1 (LBN) (Rt1(1)n) secondary heart allograft survival was prolonged indefinitely in CyS-treated Lewis (Rt1(1] recipients while ACI (Rt1a) grafts were ultimately rejected despite maintenance use of CyS. However, graft survival was significantly prolonged in these latter experiments with mean survival times (MSTs) of 29.4 +/- 32.1 days (CyS 10 mg/kg/day) and 19.4 +/- 21.1 days (CyS 15 mg/kg/day) compared to both untreated second-set controls (MST of 3.9 +/- 0.8 days, P less than 0.05), and untreated primary graft recipients (MST of 6.9 +/- 0.4 days, P less than 0.05). An attempt to identify suppressor cells in the long-term Lewis recipients of LBN hearts using an adoptive transfer experiment was unsuccessful when the spleen donors were still receiving CyS. Conversely, in a control experiment using spleens from CyS prolonged primary graft recipients in which splenectomy was performed after cessation of CyS, subsequent adoptive transfer did significantly prolong test heart graft survival in three of seven rats suggesting that suppressor cells may have been present. These data suggest that CyS is an effective immunosuppressant in presensitized hosts when MHC disparity is incomplete but that it cannot indefinitely prevent rejection in donor-recipient combinations that are completely mismatched at the MHC. Moreover, they suggest that splenic suppressor cells may not be present in animals concurrently receiving CyS.