Thomas A. Gonwa

Metabolic effects of urinary diversion of exocrine secretions in pancreatic transplantation.

We have compared the metabolic consequences of two forms of exocrine drainage for pancreaticoduodenal transplant, duodenojejunostomy (DJ) and duodenocystostomy (DC). DC offered the advantage of avoiding opening of the recipient small intestine with its potential for wound sepsis, as well as a reliable method for early detection of pancreatic rejection as measured by an abrupt fall in urinary amylase and bicarbonate concentration. However, DC led to a large urinary loss of bicarbonate with a concomitant mild metabolic acidosis. During periods of renal dysfunction, the patients with DC developed severe hyperchloremic acidosis. Use of DC for pancreatic exocrine diversion may require patients to take supplemental bicarbonate even with a well-functioniong renal transplant.

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.

Hybrid Ia antigens in man: detection with cytotoxic T cell clones

There are three known groups of human Ia antigens; HLA-DR, HLA-DQ (formerly DC or DS), and HLA-DP (formerly SB). This study investigates whether gene complementation opertes in the expression of human Ia antigens. Epstein Barr Virus (EBV) lymphoblastoid cell lines were produced from the peripheral blood mononuclear cells of a family unit (both parents and a child). Cytotoxic T cell (CTL) clones were raised against the EBV lymphoblastoid cell line of the child utilizing lymphocytes from an unrelated donor. These clones were then screened for activity against the EBV lymphoblastoid cell lines derived from both parents. Two stable CTL clones were identified that exhibited CTL activity predominantly against the child and not against either parent. Both clones were T3+, T4+, T8-, Dr+, DQ+, The activity of one of the clones was completely blocke by anti-HLA-DQ reagents but not by an anticlass-I, or an anti-HLA-DR, reagent. The other clone was blocked by a polyspecific anti-Ia reagent but not by an anti-class-I, anti-HLA-Dr, or anti-HLA-DQ reagents. These studies sugest that gene complementation plays a role in human Ia antigen expression, producing hybrid Ia antigens in a child that are not present in either parent.