C. U. Casciani

Immunosuppression without prednisone after liver transplantion is safe and associated with normal early graft function: preliminary results of a randomized study.

Abstract Prednisone has been commonly considered the mainstay of immunosuppressive therapy after liver transplantation. Recent data suggest that prednisone withdrawal late after transplant reduces complications without affecting graft function. We report here the preliminary results of an open‐label, randomized study aimed at investigating whether prednisone therapy can be completely avoided during the first 3 months after transplantation. Twenty‐seven consecutive patients were randomized to receive double (group A: cyclosporine and azathioprine) or triple (group B: prednisone, cyclosporine, and azathioprine) immunosuppressive therapy after liver transplantation. Six patients died within the first 3 weeks in each group and were excluded from the calculations. The present results refer to 10 patients in group A and 11 in group B. The actuarial 1‐year survival did not differ between the two groups (90.9 % vs 88.8 %). There were no differences with respect to infectious complications or episodes of histological acute graft rejections. Only one severe acute rejection occurred in group A and two in group B. During the first month after transplant, liver and kidney functions tended to be better in the group of patients treated without prednisone, although there were no differences in the mean cyclosporine blood levels. These data, though preliminary, indicate that early immunosuppression without the use of prednisone is safe and tends to be associated with improved liver and renal functions compared to conventional triple therapy.

Posttransplant donor-specific antibody characterization and kidney graft survival.

Abstract This study was designed to investigate the clinical relevance of donor‐specific antibodies (DS‐Abs) and their influence on graft survival. Among 106 patients who underwent cadaveric kidney donor transplantation and were monitored by flow cytometry crossmatch (FCXM) during the 1st posttransplantation year, 25 (23.6%) resulted positive for DS‐Ab production. During a 2‐year follow up only 12 of the 81 FCXM‐negative patients (14.8%) suffered rejection vs 17 of 25 FCXM‐positive patients (68%; P = 0.00001). Correlating graft loss to DS‐Ab production, 9 FCXM‐positive patients lost the graft vs only 1 among the FCXM‐negative patients. A worse graft function was evidenced in FCXM‐positive subjects who had also suffered rejection episodes than in those which had acute rejection but did not produce DS‐Abs. A high incidence of HLA‐AB mismatches was found in FCXM‐positive subjects which produced anti‐class I antibodies. FCXM appears useful in estimating post‐transplant alloimmune response. Moreover our findings confirm the harmful effects of anti‐class IDS‐Abs on long‐term graft survival.

Kidney transplant monitoring by anti donor specific antibodies.

Donor-specific anti-HLA antibodies were studied by cytotoxicity crossmatching (CTXM) and flow cytometry crossmatching (FCXM) in 117 kidney transplant candidates; the same study was carried out in 33 cadaver-donor kidney recipients, during the first 3 post-transplant months, for which donor cells were available. Pre-transport evaluation showed that 82.9% of subjects were CTXM negative/FCXM negative, 6.8% of patients were positive in both tests, and 10.3% were CTXM negative/FCCM positive. Post-transplant monitoring for donor-specific antibodies (Abs-DS) showed that nine recipients (27.3%) were FCXM positive; six of them were IgG+ and three IgM+. In comparing these results with the clinical course, a significant association between FCXM IgG+ and rejection episodes was observed (P < 0.01).

CHRONIC RENAL FAILURE FOLLOWING ORTOTOPIC LIVER TRANSPLANTATION: AN EPIDEMIOLOGICAL STUDY.

CHRONIC RENAL FAILURE FOLLOWING ORTOTOPIC LIVER TRANSPLANTATION: AN EPIDEMIOLOGICAL STUDY. G. Splendiani, G. Tisone, C. Meloni, S. Cipriani, L. De Luca, S. Dominijanni, E. Straccialano, A. Vega, S. Condò, C.U. Casciani Nephrology and Dialysis Dept., General Hospital, “Tor Vergata” University, Rome, Italy, Surgical Clinic Dept., “Tor Vergata” University, Rome, Italy, Nephrology and Dialysys Unit, “S.Eugenio” Hospital, Rome, Italy, Chair of Nephrology, “Tor Vergata” University, Rome, Italy

Gangliosides potentiate the immunosuppressive effects of cyclosporin A in rat skin allografts

In vitro gangliosides exert inhibitory effects on cellular immune responses, largely relying on an impairment of the IL-2/IL-2 receptor interaction. In a previous study we have demonstrated synergistic effects of gangliosides and cyclosporin A (CyA) in the inhibition of the generation of in vitro allospecific immune responses in humans. To evaluate the possibility of using these drugs in immunosuppressive therapy in organ transplantation, we investigated the effects of the combination of a gangliosides mixture (GAMIX) and suboptimal doses of CyA on rat skin allografts in vivo. Sprague-Dawley rats were implanted with skin grafts from Lewis rats and treated for 21 days by intraperitoneal administration of either GAMIX or CyA or a combination of the two drugs. Untreated, GAMIX-treated or CyA-treated rats rejected skin allografts. In contrast, when a combined GAMIX CyA treatment was administered, successful grafting could be obtained in 8 rats out of 10 tested. Cells derived from spleens on day 21 post graft were stimulated in vitro with PWM mitogen. We found that cells from transplanted rats, untreated or treated with low-dose CyA or GAMIX alone, showed comparable responses to PWM. Cells from rats treated with the combination of the two drugs were found to be virtually unresponsive to stimulation by PWM mitogen. Taken together, our results indicate that GAMIX potentiate in vivo and ex vivo immunosuppressive effects of low-dose CyA.