Prolonged Action of a Chimeric Interleukin-2 Receptor (Cd25) Monoclonal Antibody Used in Cadaveric Renal Transplantation

Amlot, Peter; Rawlings, E.; Fernando, Ossie N.; Griffin, Peter; Heinrich, Günther; Schreier, Max H.; Castaigne, Jean‐Paul; Moore, Richard H.; Sweny, P.

doi:10.1097/00007890-199510150-00023

Cited by 174 publications

(97 citation statements)

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“…The predomi-nant role of the IL-2/IL-2R pathway in the proliferation of T lymphocytes, together with the selective expression of CD25 on activated lymphocytes, led to the concept that inhibition of CD25 could reduce the incidence of acute rejection episodes. 11 The recent development of chimeric monoclonal antibodies with mouse variable regions and human constant regions has reduced the problems of immunogenicity associated with murine monoclonal antibodies 12,13 while maintaining the high affinity toward CD25 of the original murine antibody.…”

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confidence: 99%

“…13 Basiliximab binds to the ␣ chain of the IL-2R (IL-2R␣) with an affinity approximating that of IL-2 itself and therefore is a potent inhibitor of IL-2-mediated T-cell proliferation. Resting T cells, which do not express IL-2R␣, are not affected.…”

mentioning

confidence: 99%

“…Early clinical studies 13,14 have shown that basiliximab is well tolerated, with no evidence of significant immunogenicity. These and other studies 15 also have shown that optimal administration of basiliximab is 20 mg intravenously the day of transplantation, followed by a second intravenous dose day 4 after transplantation.…”

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confidence: 99%

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Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Calmus

2002

Liver Transplantation

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Acute graft rejection remains a major problem among additional sequelae in liver transplant recipients. Basiliximab, a chimeric monoclonal antibody with high affinity for the CD25 chain of the interleukin-2 receptor, has significantly reduced the incidence of acute rejection episodes in renal transplant recipients. This single-arm, open-label, multicenter study investigated the efficacy and tolerability of basiliximab immunoprophylaxis in adult patients undergoing first elective liver transplantation. One hundred one patients (70 hepatitis C virus [HCV]-negative patients, 31 HCV-positive patients) were administered basiliximab, 20 mg, by intravenous bolus injection the day of transplantation (day 0) and day 4. In addition, all patients were administered triple immunosuppressive therapy with cyclosporine, steroids, and azathioprine. The efficacy of basiliximab was assessed by conventional parameters, and tolerability was assessed by the incidence of adverse events, infections, and laboratory test result abnormalities. At 6 months, the incidence of first acute biopsy-confirmed rejection episodes was 22.8%. Rejections were more frequent in the HCV-positive (29.0%) than HCV-negative subgroup (20.0%; P ‫؍‬ .441). No rejection episode was graded histologically as severe, and no patient required antibody therapy for the management of acute rejection. Ten patients (9.9%) required treatment with tacrolimus for acute rejection episodes. Patient and graft survival rates at 12 months were 90.1% and 88.1%, respectively. Basiliximab caused no injection-site reactions, anaphylaxis, or cytokine release syndrome. Five malignancies were reported at 12 months: of these, three malignancies predated transplantation surgery. Compared with earlier studies, the addition of basiliximab immunoprophylaxis to triple immunosuppressive therapy provides increased efficacy in reducing the incidence of acute rejection episodes, with no clinically significant increase in adverse events. (Liver Transpl 2002;8: 123-131.)

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Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Calmus

2002

Liver Transplantation

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“…For example, Th1 cells produce IFN-g, which can inhibit Th2 cell development and humoral immunity, while Th2 cells produce IL-4 and IL-10, which can inhibit Th1 cell development, activation, and the activation and bactericidal capacity of MФ. Some studies have shown that Th1 is highly expressed during rejection, whereas Th2 is expressed mainly during tolerance or long-term acceptance of transplanted organs (Amlot et al, 1995;Quiroga et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…At the gene level, CsA inhibits the production and release of IL-2 and IFN-γ (Grinyo et al, 2004;Zhang et al, 2007). IL-2 is a growth factor that is correlated with T cell survival, differentiation, and proliferation (Amlot et al, 1995), and IFN-γ is a critical factor (Quiroga et al, 2000) promoting Th1 cell differentiation. Kovarik et al (1996) showed that CsA could stimulate promoter activity of the transforming growth factor-b (TGF-b) gene, thereby increasing TGF-γ expression.…”

Section: Discussionmentioning

confidence: 99%

Changes in peripheral blood Th1 and Th2 cells in rat liver transplantation under different immune statuses

Yang¹,

Cheng²,

Sun³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. In this study, early expressions of peripheral blood Th1 and Th2 cells were documented following rat liver transplantation and related to immune status. Rats were divided into 3 groups: group A (control): syngeneic transplantation (Brown Norway (BN) → BN); group B: allogeneic transplantation + cyclosporine A (CsA); group C: allogeneic transplantation (Lewis → BN). Flow cytometry was used to analyze peripheral blood CD4 + CD45RC percentage on days 1, 3, 5, 7, and 14 following transplantation, and were compared to graft rejection pathological grades and receptor survival times. The average survival of groups A and B exceeded 100 days, which was significantly longer than that of group C (3.56 ± 34.3 days). With the exception of the first day, rejection grades were significantly higher in groups C and B compared to group A, and group C rejection grades were significantly higher than those of group B. Three days after transplantation, the CD4 + CD45RC + to CD4 + CD45RC -ratio of group C was significantly higher than that of groups A and B. In group B, the CD4 + CD45RC + to CD4 + CD45RC -ratio was negatively correlated to the rejection grade (r = -0.565, P < 0.01), whereas this relationship was positive in group C (r = 0.745, P < 0.01). In conclusion, peripheral blood Th1 was highly expressed during rejection in rat liver grafts. Peripheral blood Th2 tended to increase early under rejection inhibition with CsA, and its high expression level may correlate with long-term acceptance or tolerance of transplanted livers.

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Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus disease after renal transplantation

et al. 1997

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Studies have shown that risk factors for human cytomegalovirus (HCMV) disease after renal transplant include primary infection (virus of donor origin infecting a non-immune individual), re-infection (virus of donor origin infecting a immune individual), and the detection of viraemia (as a marker of virus dissemination). We now report that viral load in the urine is also a significant factor in HCMV disease and is one of the main mechanisms underlying the risk associated with viraemia and donor serostatus. Longitudinal analysis of a group of 196 renal recipient identified 35 recipients who were PCR positive for HCMV in urine. Elevated viral loads were present in symptomatic patients, viraemic patients, and patients experiencing primary HCMV infection. Disease was associated with the peak quantity of virus present in the urine during the post-transplant period (P = 0.0001), with viraemia (P = 0.0003), and with transplantation of a seropositive donor (P = 0.03). Univariate logistic regression analysis showed that increases of 0.25 log10 in viral load were associated with a 179% increased risk of disease (odds ratio = 2.79; 95% C.I. 1.22-6.39; P = 0.02). This effect persisted in a multivariate logistic analysis when viraemia was incorporated (odds ratio = 2.77; 95% C.I. 1.07-7.18; P = 0.04). In contrast, the significant association between viraemia and disease observed in univariate analysis (odds ratio = 23.75; 95% C.I. 3.69-152.90; P = 0.0009) became marginally non-significant in multivariate analysis once viral load had been controlled for (odds ratio = 34.54; 95% C.I. 0.75-1599.00; P = 0.07). The computed probability of disease showed that a rapid transition occurred at viral loads between 10(5.7) and 10(6.5) genomes/ml urine in non-viraemic patients compared to viral loads between 10(5.0) and 10(5.7) genomes/ml urine in patients with concurrent viraemia. The implications of these findings for understanding HCMV pathogenesis, improving patient management, and optimising trials of antiviral treatment are discussed.

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Prolonged Action of a Chimeric Interleukin-2 Receptor (Cd25) Monoclonal Antibody Used in Cadaveric Renal Transplantation

Cited by 174 publications

References 0 publications

Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Immunoprophylaxis with basiliximab, a chimeric anti[ndash ]interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients

Changes in peripheral blood Th1 and Th2 cells in rat liver transplantation under different immune statuses

Quantity of cytomegalovirus viruria is a major risk factor for cytomegalovirus disease after renal transplantation

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